Molecular orbital calculations of ring opening of the isoelectronic cyclopropylcarbinyl radical, cyclopropoxy radical, and cyclopropylaminium radical cation series of radical clocks

Detailed molecular orbital calculations were directed to the cyclopropylcarbinyl radical (1), the cyclopropoxy radical (2), and the cyclopropylaminium radical cation (3) as well as their ring-opened products. Since a considerable amount of data are published about cyclopropylcarbinyl radicals, calculations were made for this species and related ring-opened products as a reference for 2 and 3 and their reactions. Radicals 1-3 have practical utility as "radical clocks" that can be used to time other radical reactions. Radical 3 is of further interest in photoelectron-transfer processes where the back-electron-transfer process may be suppressed by rapid ring opening. Calculations have been carried out at the UHF/6-31G*, MP4//MP2/6-31G*, DFT B3LYP/6-31G*, and CCSD(T)/cc-pVTZ//QCISD/cc-pVDZ levels. Energies are corrected to 298 K, and the barriers between species are reported in terms of Arrhenius E(a) and log A values along with differences in enthalpies, free energies, and entropies. The CCSD(T)-calculated energy barrier for ring opening of 1 is E(a) = 9.70, DeltaG* = 8.49 kcal/mol, which compares favorably to the previously calculated value of E(a) = 9.53 kcal/mol by the G2 method, but is higher than an experimental value of 7.05 kcal/mol. Our CCSD(T)-calculated E(a) value is also higher by 1.8 kcal/mol than a previously reported CBS-RAD//B3LYP/6-31G* calculation. The cyclopropoxy radical has a very small barrier to ring opening (CCSD(T), E(a) = 0.64 kcal/mol) and should be a very sensitive time clock. Of the three series studied, the cyclopropylaminium radical cation is most complex. In agreement with experimental data, bisected cyclopropylaminium radical cation is not found, but instead a ring-opened species is found. A perpendicular cyclopropylaminium radical cation (4) was found as a transition-state structure. Rotation of the 2p orbital in 4 to the bisected array results in ring opening. The minimum onset energy of photoionization of cyclopropylamine was calculated to be 201.5 kcal/mol (CCSD(T)) compared to experimental values of between about 201 and 204 kcal/mol. Calculations were made on the closely related cyclopropylcarbinyl and bicyclobutonium cations. Stabilization of the bisected cyclopropylcarbinyl conformer relative to the perpendicular species is much greater for the cations (29.1 kcal/ mol, QCISD) compared to the radicals (3.10 kcal/mol, QCISD). A search was made for analogues to the bicyclobutonium cation in the radical series 1 and 2 and the radical cation series 3. No comparable species were found. A rationale was made for some conflicting calculations involving the cyclopropylcarbinyl and bicyclobutonium cations. The order of stability of the cyclopropyl-X radicals was calculated to be X = CH2 > X = O > X = NH2+, where the latter species has no barrier for ring opening. The relative rate of ring opening for cyclopropyl-X radicals X = CH2 to X = O was calculated to be 3.1 x 10(6) s(-1) at 298 K (QCISD).     

Synthesis of block copolymers from polyvinyl chloride prepared in the presence of nitroxyl radicals of the imidazoline series

Specific features of radical polymerization of vinyl chloride in the presence of nitroxyl radicals of the imidazoline series (2-methyl-2,3-diphenyl-1,4-diazaspiro[4,5]dec-3-ene-1-oxyl, 2,2,5,5-tetramethyl-4-phenyl-2,5-dihydroimidazole-1-oxyl, 2,2,5-trimethyl-4,5-diphenyl-2,5-dihydroimidazole-1-oxyl) were studied. The possibility of preparing vinyl chloride-styrene block copolymers in the presence of these nitroxyl radicals was demonstrated, suggesting the occurrence of the polymerization by the reversible inhibition mechanism. The molecular-mass characteristics and the glass transition points of the synthesized samples were determined.     

Ring opening versus ring expansion in rearrangement of bicyclic cyclobutylcarbinyl radicals

Ring opening and expansion of multicyclic cyclobutylcarbinyl radicals provides an appealing method for the construction of heavily substituted ring systems in a stereocontrollable fashion. Here we conducted the first, systematic study on the regioselectivity in the rearrangement of various synthetically relevant cyclobutylcarbinyl radicals. It was found that a two-layer ONIOM method, namely ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(2df,2p)), could accurately predict the free energy barriers of the ring openings of cyclobutylcarbinyl radicals with a precision of 0.3 kcal/mol. By using this powerful tool we found that the regiochemistry for the ring opening of monocyclic cyclobutylcarbinyl radicals could be easily predicted by the relative stability of the two possible carbon radical products. A linear correlation was found between the activation and reaction free energies. This observation indicated that the ring opening of cyclobutylcarbinyl radicals was strongly affected by the thermodynamic factors. On the basis of the above results we extended our study to the rearrangement of bicyclic cyclobutylcarbinyl radicals that could undergo both ring opening and expansion. It was found that for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the bridge methyl group, ring expansion was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring adjacent to the bridge methyl group. On the other hand, for bicyclic cyclobutylcarbinyl radicals whose radical center was located at the 2-position, ring opening was the favored rearrangement pathway unless a strongly radical-stabilizing substituent was placed in the cyclobutyl ring at the bridge position.     

Rate constants for reactions of alkyl radicals with water and methanol complexes of triethylborane

Reactions of secondary alkyl radicals with triethylborane and several of its complexes were studied. The H-atom transfer reactions from Et3B-OH2 and Et3B-OD2 were suppressed by addition of pyridine to the reaction mixture. Rate constants for reactions of secondary alkyl radicals with triethylborane and its complexes with water, deuterium oxide, methanol, and THF at ambient temperature were determined by radical clock methods. Cyclization of the 1-undecyl-5-hexenyl radical and ring opening of the 1-cyclobutyldodecyl radical were evaluated as clock reactions. The cyclobutylcarbinyl radical ring opening had the appropriate velocity for relatively precise determinations of the ratios of rate constants for H-atom transfer trapping and rearrangement, and these ratios combined with an estimated rate constant for the cyclobutylcarbinyl radical ring opening gave absolute values for the rate constants for the H-atom transfer reactions. For example, the triethylborane-water complex reacts with a secondary alkyl radical in benzene at 20 degrees C with a rate constant of 2 x 10(4) M(-1) s(-1). Variable temperature studies with the Et3B-CH3OH complex in toluene indicate that the hydrogen atom transfer reaction has unusually high entropic demand, which results in substantially more efficient hydrogen atom transfer trapping reactions in competition with radical ring opening and cyclization reactions at reduced temperatures.     

Nitroxyl radicals of the imidazoline series as agents of pseudoliving polymerization of styrene

Radical polymerization of styrene in the presence of 2,2,4,5,5-pentamethyl-2,5-dihydro- Imidazol-1-oxyl, 2,2-diethyl-4,5,5-trimethyl-2,5-dihydroimidazol-1-oxyl, 2,2,5,5-tetramethyl- 4-phenyl-2,5-dihydroimidazol-1-oxyl, 2,2,5-trimethyl-4,5-diphenyl-2,5-dihydroimidazol- 1-oxyl, and 2-methyl-2,3-diphenyl-1,4-diazaspiro[4.5]deca-3-en-1-oxyl was studied. Effect of substituents in the nitroxyl radical and the nature of initiator on the features of “pseudoliving” polymerization and the molecular-weight characteristics of polystyrene synthesized were considered. Nitroxyl radicals of imidazoline series, like TEMPO and its derivatives, allow one to regulate polymerization of styrene and obtain polymers with relatively low values of polydispersity index.     

Substituent effects on the ring opening of 2-aziridinylmethyl radicals

[reaction: see text] Substituent effects on the ring-opening reactions of 2-aziridinylmethyl radicals were studied systematically for the first time utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was found that various substituents on the nitrogen atom had a relatively small effect on the ring opening of the 2-aziridinylmethyl radical. A pi-acceptor substituent at the C(1) position reduced the energy barrier for C-C cleavage dramatically, but it increased the energy barrier for C-N cleavage significantly at the same time. When the C(1) substituent is alkyl, the ring opening should always strongly favor the C-N cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is CHO (or CO-alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) substituent is aryl (or alkenyl or alkynyl), the ring opening should favor the C-C cleavage pathway if the N substituent is alkyl or COR. If both the C(1) substituent and the N substituent are aryl, the ring opening should proceed via both the C-C and C-N cleavage pathways. The solvent effect on the regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found to be very small. The substituent effects on C-C cleavage could be explained successfully by the spin-delocalization mechanism. For the substituent effects on C-N cleavage, an extraordinary through-bond pi-acceptor effect must be taken into account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that the ring strain could also affect the regiochemistry of the ring-opening reactions.     

Effect of substituents on the stabilities of multiply-substituted carbon-centered radicals

The bond dissociation energies (BDEs) and radical stabilization energies (RSEs) which result from 166 reactions that lead to carbon-centered radicals of the type ˙CH(2)X, ˙CHXY and ˙CXYZ, where X, Y and Z are any of the fourteen substituents H, F, Cl, NH(2), OH, SH, CH[double bond, length as m-dash]CH(2), C[triple bond, length as m-dash]CH, BH(2), CHO, COOH, CN, CH(3), and CF(3), were calculated using spin-restricted and -unrestricted variants of the double-hybrid B2-PLYP method with the 6-311+G(3df,2p) basis set. The interactions of substituents X, Y, and Z in both the radicals (˙CXYZ) and in the precursor closed-shell molecules (CHXYZ), as well as the extent of additivity of such interactions, were investigated by calculating radical interaction energies (RIEs), molecule interaction energies (MIEs), and deviations from additivity of RSEs (DARSEs) for a set of 152 reactions that lead to di- (˙CHXY) and tri- (˙CXYZ) substituted carbon-centered radicals. The pairwise quantities describing the effects of pairs of substituents in trisubstituted systems, namely pairwise MIEs (PMIEs), pairwise RIEs (PRIEs) and deviations from pairwise additivity of RSEs (DPARSEs), were also calculated for the set of 61 reactions that lead to trisubstituted radicals (˙CXYZ). Both ROB2-PLYP and UB2-PLYP were found to perform quite well in predicting the quantities related to the stabilities of carbon-centered radicals when compared with available experimental data and with the results obtained from the high-level composite method G3X(MP2)-RAD. Particular selections of substituents or combinations of substituents from the current test set were found to lead to specially stable radicals, increasing the RSEs to a maximum of +68.2 kJ mol(-1) for monosubstituted radicals ˙CH(2)X (X = CH[double bond, length as m-dash]CH(2)), +131.7 kJ mol(-1) for disubstituted radicals ˙CHXY (X = NH(2), Y = CHO), and +177.1 kJ mol(-1) for trisubstituted radicals ˙CXYZ (X = NH2, Y = Z = CHO).     

Photolysis and oxidation of azidophenyl-substituted radicals: delocalization in heteroatom-based radicals

2-(4-Azidophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (14), 2-(4-azidophenyl)benzimidazole-1-oxide-3-oxyl (16), 2-(4-azidophenyl)-1,2,6-triphenylverdazyl (19), 2-(3-azidophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (21), and (3-azidophenyl)-N-tert-butyl-N-aminoxyl (25) were photolyzed in frozen solution to give S = 3/2 state ESR spectra of the corresponding nitrenophenyl radicals with the following zero-field splitting parameters: |D/hc| = 0.277 cm(-1), |E/hc| < or = 0.002 cm(-1) (7 from 14); |D/hc| = 0.256 cm(-1), |E/hc| < or = 0.002 cm(-1) (8 from 16); |D/hc| = 0.288 cm(-1), |E/hc| < or = 0.002 cm(-1) (9 from 19); |D/hc| = 0.352 cm(-1), |E/hc| = 0.006 cm(-1) (10 from 21); |D/hc| = 0.336 cm(-1), |E/hc| = 0.004 cm(-1) (11 from 25). UB3LYP/6-31G computations and ESR spectroscopic analyses suggest that these are nitreno radicals, even para-linked systems with possible quinonoidal resonance forms. Neat samples of azidophenyl radicals 14 and 21 showed bulk paramagnetic behavior, consistent with the lack of close contacts in their crystal structures. Efforts to make photolabile coordination complexes of 14 and 21 with paramagnetic transition metal ions were unsuccessful: Cu(ClO4)2 x 6H2O instead oxidized them to the corresponding diamagnetic nitrosonium perchlorate salts.     

One-electron oxidation of ferrocenes by short-lived N-oxyl radicals. The role of structural effects on the intrinsic electron transfer reactivities

A kinetic study of the one electron oxidation of substituted ferrocenes (FcX: X = H, COPh, COMe, CO(2)Et, CONH(2), CH(2)OH, Et, and Me(2)) by a series of N-oxyl radicals (succinimide-N-oxyl radical (SINO), maleimide-N-oxyl radical (MINO), 3-quinazolin-4-one-N-oxyl radical (QONO) and 3-benzotriazin-4-one-N-oxyl radical (BONO)), has been carried out in CH(3)CN. N-oxyl radicals were produced by hydrogen abstraction from the corresponding N-hydroxy derivatives by the cumyloxyl radical. With all systems, the rate constants exhibited a satisfactory fit to the Marcus equation allowing us to determine self-exchange reorganization energy values (λ(NO˙/NO(-))) which have been compared with those previously determined for the PINO/PINO(-) and BTNO/BTNO(-) couples. Even small modification of the structure of the N-oxyl radicals lead to significant variation of the λ(NO˙/NO(-)) values. The λ(NO˙/NO(-)) values increase in the order BONO < BTNO < QONO < PINO < SINO < MINO which do not parallel the order of the oxidation potentials. The higher λ(NO˙/NO(-)) values found for the MINO and SINO radicals might be in accordance with a lower degree of spin delocalization in the radicals MINO and SINO and charge delocalization in the anions MINO(-) and SINO(-) due to the absence of an aromatic ring in their structure.     

Photolysis of 1-alkylcycloalkanols in the presence of (diacetoxyiodo)benzene and I2. Intramolecular selectivity in the beta-scission reactions of the intermediate 1-alkylcycloalkoxyl radicals

The C-C beta-scission reactions of 1-alkylcycloalkoxyl radicals, generated photochemically by visible light irradiation of CH2Cl2 solutions containing the parent 1-alkylcycloalkanols, (diacetoxy)iodobenzene (DIB), and I2, have been investigated through the analysis of the reaction products. The 1-alkylcycloalkoxyl radicals undergo competition between ring opening and C-alkyl bond cleavage as a function of ring size and of the nature of the alkyl substituent. With the 1-propylcycloheptoxyl, 1-propylcyclooctoxyl,and 1-phenylcyclooctoxyl radicals, formation of products deriving from an intramolecular 1,5-hydrogen atom abstraction reaction from the cycloalkane ring has also been observed. The results are discussed in terms of release of ring strain associated to ring opening, stability of the alkyl radical formed by C-alkyl cleavage, and with cycloheptoxyl and cyclooctoxyl radicals, also in terms of the possibility of achieving a favorable geometry for intramolecular hydrogen atom abstraction.     

Alpha- and beta-thujone radical rearrangements and isomerizations. A new radical clock

Radical clocks have been extensively used in chemical and biochemical mechanistic studies. The C4 radicals of alpha- and beta-thujone can undergo two distinct rearrangement reactions that could, in principle, serve as simultaneous but independent radical clocks. We have therefore generated these C4 radicals by photolysis of the corresponding N-hydroxypyridine-2-thione ester precursors and have investigated their fates and lifetimes. Photolysis of either alpha- or beta-thujone generates the same 6:100 mixture of alpha- and beta-thujone when the radicals are quenched by thiophenol. Hydrogen atom transfer from thiophenol to the radical thus occurs preferentially from the less sterically hindered alpha-face to give beta-thujone. The third product formed in the photolysis via opening of the cyclopropyl ring is 2-methyl-5-isopropylcyclopent-2-enone. The ratio of ring opened to unopened products gives very similar values of kralpha = 4.4 x 10(7) s(-1) and krbeta = 1.0 x 10(8) s(-1) for ring opening of the radicals generated from alpha- and beta-thujone, respectively. If the C4 cation rather than radical is generated, it is converted to carvacrol, a phenol that is not obtained in the radical reactions. Thujone therefore differentiates between radical and cation pathways and provides a measure of the radical lifetime.     

XPS spectra of free nitroxyl radicals and their electronic structure

The N(1s) and O(1s) XPS spectra of stable nitroxyl radicals and molecules with a related heterocycle structure: 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(3-nitrophenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxyphenyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl, 4,4,5,5-tetramethyl-2-(2-hydroxy-3-nitrophenyl)-4,5-dihydro-1Himidazole-3-oxide-1-oxyl, and 4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-1H-imidazole-3-oxide were studied. The possibility to apply X-ray electron spectra for investigation of the charge electron and spin density distribution on free radical atoms and at their coordination by a metal is considered.     

An electron spin resonance study of radicals from chloramine-t-1 : Spin trapping of radicals produced in acid media

Under acid conditions aqueous solutions of chloramine-T form nitrogen-centred radicals via loss of the chlorine atom. The nitrogen radicals produced have been studied by ESR spectroscopy using the spintrapping method. Adducts of the spin trap phenyl-t-butyl nitrone are oxidized by chloramine-T in acid media to give a paramagnetic product in which the unpaired electron interacts with two inequivalent nitrogen atoms. The spin trap 5,5-dimethyl-2-pyrrolidine-1 -oxide is oxidized rapidly to 5,5-dimethyl-2-pyrrolidone-1-oxyl by chloramine-T under acid onditions. The water soluble trap α-4-pyridyl-1-oxide-N-t-butyl nitrone forms a stable nitroxide adduct with a nitrogen radical of chloramine-T in acid solution. Identical results were obtained with chloramine-B (sodium salt of N-chlorobenzene sulfonamide), indicating the involvement of the N-chloramine group in radical formation.     

N-Alkenyl-2-aziridinylmethyl radicals and N-alkenylaminyl radicals in cascade cyclizations to pyrrolizidines and indolizidines

[reaction: see text] The radical cascade cyclizations of N-alkenyl-2-aziridinylmethyl radicals to pyrrolizidines and indolizidines were examined using density functional theory (DFT) calculations. A large preference for cyclization to pyrrolizidines was found. These predictions corroborated very well with experimental results, leading to an efficient synthesis of pyrrolizidines. No radical cascade cyclization to indolizidines could be performed in practice as only ring opening of N-alkenyl-2-aziridinylmethyl radicals to N-allyl-N-alkenylamines occurred.     

Interaction of chlorine dioxide with nitroxyl radicals

The formation of charge transfer complexes between chlorine dioxide and nitroxyl radicals (2,2,6,6-tetramethylpiperidin-1-oxyl, 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-oxo-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-methoxy-2,2,6,6-tetramethylpiperidin-1-oxyl, 4-acetylamido-2,2,6,6-tetramethylpiperidin-1-oxyl, 2,2,5,5-tetramethyl-4-phenyl-3-imidazolin-1-oxyl, and bis(4-methoxyphenyl) nitroxide) in acetone, acetonitrile, n-heptane, diethyl ether, carbon tetrachloride, toluene, and dichloromethane was found by spectrophotometry at –60—+20 °C. The thermodynamic parameters of complex formation were determined. The radical structure affects its complex formation ability. The charge transfer complex is transformed into the corresponding oxoammonium salt.     

Rearrangements of free radicals x : C7H7 - radicals and related systems

7-Norbornadienyl radical rearranges in matrix to tropylium radical. Deuterated and cyano substituted bicyclo(3.2.0)heptadienyl radicals do not undergo 1.2-vinyl shifts prior to electrocyclic ring opening.     

Nitroxyl radical reactions with 4-pentenyl- and cyclopropylketenes: new routes to 5-hexenyl- and cyclopropylmethyl radicals

4-Pentenylketenes 4a and 9 and cyclopropylketenes 3a, 13, 14 (RCH=C=O) are generated by photochemical Wolff rearrangements and observed by IR as relatively long-lived species at room temperature in hydrocarbon solvents. The reactions of these ketenes with the nitroxyl radicals tetramethylpiperidinyloxyl (TEMPO, TO*) and tetramethylisoindoline-2-oxyl (TMIO, IO*) form carboxy substituted 5-hexenyl and cyclopropylmethyl radicals which are either trapped by a second nitroxyl radical or undergo rearrangements followed by trapping. The rate constant of the reaction of 4a with TEMPO was similar to that of n-BuCH=C=O (1b), while 3a was 4.3 times more reactive, indicating cyclopropyl stabilization of the incipient radical.     

Electron impact fragmentation of some mixed cyclotetraphosphazenes

The electron impact fragmentations of some cyclotetraphosphazenes are reported and discussed. The major fragmentation path involves loss of two amine radicals and one chlorine radical in the series P₄N₄Cl_8-n(NMe₂)_n when n=2, and subsequent stages involve a ring contraction process with elimination of a P = N fragment, when n = 5 loss of amine radicals predominates on statistical grounds with little evidence of ring contraction. In the series P₄N₄F_8-n(NMe₂)_n fragmentation is dominated by loss of amino radicals when n = 4 and loss of fluorine radicals predominates on statistical grounds when n = 2. In the series P₄N₄F_8-nX_n (n = 2 or 4, X = Cl or Br), when n = 2 and X = Br the major fragmentation path is the loss of two bromine radicals, whereas when X = Cl the more favoured path is the loss of two chlorine radicals. In both, subsequent stages involve ring contraction reactions with elimination of a PN fragment. When n = 4 and X = Br or Cl on bond energy grounds the more favoured fragmentation pattern is the loss of bromine or chlorine radicals, respectively.     

Dimerization of organic free radicals in solution. 1. Temperature dependent measurements

Dimerization enthalpies and equilibrium constants have been determined for the radical anion of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), the radical cations of N,N,N',N'-tetramethyl-p-phenylenediamine, N,N-dimethyl-p-phenylenediamine, 2,3,5,6-tetramethyl-p-phenylenediamine, N,N,N',N'-tetraethyl-p-phenylenediamine, N,N-diethyl-p-phenylenediamine and N,N,N'-trimethyl-p-phenylenediamine. Neutral radicals investigated are 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and galvinoxyl. Solvent used was acetone, EtOH/Et2O-mixture (2:1 volume), propionitrile/butyronitrile-mixture (1:1 M) and dichloromethane. Measured dimerization enthalpies deltaHdim vary from -72.1 to -16.6 k/mol.     

Generation and intermolecular capture of cyclopropylacyl radicals

[reaction: see text] Cyclopropylacyl radicals derived from S-cyclopropylacyl xanthates (dithiocarbonates) undergo intermolecular additions to olefins without loss of CO or ring opening. In the presence of a phenyl ring on carbon C-1 of the cyclopropane ring, loss can be made to occur in the absence of an olefinic trap. The adducts from the cyclopropylacyl radical additions are easily converted into enones by base-induced beta-elimination of the xanthate group.