Radical Truce-Smiles reactions on an isoxazole template: Scope and limitations

The use of TiCl₃-HCl as promotor in the radical Truce-Smiles reactions of 2-(((3,5-dimethylisoxazol-4-yl)sulfonyl)oxy)benzenediazonium salts has been investigated in detail. During these reactions the desired Truce-Smiles rearrangement (via an ipso-substitution reaction) is accompanied by the formation of a number of by-products including dihydrobenzo[5,6][1,2]oxathiino[3,4-d]isoxazole 4,4-dioxides, dioxidobenzo[e][1,2]oxathiin-3-yl)ethan-1-ones, anilines and chloroaromatics. Replacing TiCl₃-HCl by Cu(NO₃)₂-Cu₂O as reductant in these reactions was found to afford broadly comparable product distributions. Competition and radical clock experiments also provide an indication of the relative susceptibility of the isoxazole nucleus towards attack by aryl radicals.     

Unusual rearrangement of (cyclopropylmethoxy)benzene and its derivatives in the presence of BF<Subscript>3</Subscript>·Et<Subscript>2</Subscript>O

(Cyclopropylmethoxy)benzene and its ortho- and para-bromo-substituted analogs in the presence of BF₃ · Et₂O undergo rearrangement with formation of (cyclobutyloxy)benzene and 2-ethyl-2,3-dihydro-1-benzofuran.     

Selective 3,3-Rearrangement of Azobenzenes upon Complexation by a Frustrated Lewis Pair

The reaction of the oxygen-bridged frustrated Lewis pairs (FLPs) tBu₂P−O−Si(C₂F₅)₃ ( 1 ) and tBu₂P−O−AlBis₂ ( 2 ) with azobenzene, promoted by UV irradiation, led to a selective complexation of the cis-isomer. The addition product of 2 is stable, while the adduct of 1 isomerizes in solution in an ortho-benzidine-like [3,3]-rearrangement by cleavage of the N−N bond, saturation of the nitrogen atoms with hydrogen atoms and formation of a new bond between two phenyl ortho-carbon atoms. Similar rearrangements take place with different para-substituted azobenzenes (R=Me, OMe, Cl) and di(2-naphthyl)diazene, while ortho-methylated azo compounds do not form adducts with 1 . All adducts were characterized by multinuclear NMR spectroscopy and elemental analyses and the mechanism of the rearrangement was explored by quantum-chemical calculations.     

Methylation of Aniline Over SAPO-11

Methylation of aniline over a mildly acidic siliconaluminium phosphate catalyst (SAPO-11) with medium pores is reported. The selectivity of N-methylates products is about 90%. By comparison with results obtained from SAPO-5 with large pores and with amorphous aluminium phosphate, molecular sieves with medium pores prevent the formation of bulky isomers and better resist formation of coke. The ortho isomer is most abundant among toluidine isomers. Some ortho isomers may result from the rearrangement of N-methylaniline.     

Intramolecular aromatic substitution reactions in substituted N,N-dimethylthiobenzamide ions

The molecular ions of N,N-dimethylthiobenzamide and its ortho substituted derivatives (substituents CH₃, Cl, Br, I) lose a hydrogen atom and/or the ortho substituent. The mechanism of this process has been studied by measurements of the ionization energies, appearance energies of the product ions m/z 164 and the kinetic energy release during this process. The structure of the product ions m/z 164 and relevant reference ions have been investigated by mass analysed ion kinetic energy spectra, B/E linked scan spectra and collision induced decompositions. The results show clearly the formation of two different kinds of product ions m/z 164 depending on the substituent lost. Type a ions are formed by loss of a H atom or the CH₃ substituent and correspond to protonated 3,4-benzo-N-methylpyroline-2-thione. The formation of these ions occurs by a hydrogen rearrangement followed by an intramolecular substitution via a 5-membered cyclic intermediate and is associated with a large release of kinetic energy. In contrast, the loss of the halogeno substituents to give type b ions probably occurs via a direct displacement reaction by the sulfur atom of the thioamide group giving rise to Gaussian shaped peaks mass analysed ion kinetic energy spectra.     

One‐Pot Cascade Transformation of Glucal into Structurally Diverse Drug‐Like Scaffolds

A diversity‐oriented synthesis strategy to produce three types of structurally drug‐like N‐heterocyclic‐fused rings has been developed from abundant biomass‐derived d ‐glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino‐Nazarov cyclization was performed in one‐pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline‐fused products were readily accessible using ortho‐unsubstituted secondary anilines as substrates, reactions with ortho‐hydroxyl‐anilines furnished fused 1,4‐benzoxazines instead. In both cases, InBr₃ acted as the Lewis acid catalyst. By altering InBr₃ to Ln(OTf)₃, the indoline‐fused products could be further converted into tetrahydroquinoline‐fused cyclopentenones via ensuing retro‐ene rearrangement.     

A study of the ortho effects and rearrangement processes in the mass spectra of 2-arylaminothiazine and -thiazoline derivatives

The behaviour of the title compounds under electron impact has been investigated using low and high resolution mass spectrometry and partial ¹⁵N and D labelling. A number of ions produced by rearrangement were observed. Abundant ions are formed by intramolecular ortho substitution reactions (cyclizations), as demonstrated by energetic and kinetic considerations and by studying the decomposition pathways of these ions. The ortho substitution processes involve loss or rearrangement of an ortho group of the aromatic ring.     

Claisen aromatic amino rearrangement in the series of fluorinated anilines

The effect ofmeta-substituents in the aromatic ring on the route of Claisen rearrangement ofN-(pent-3-en-2-yl)-3-fluoro(or 3-trifluoromethyl, 3,4-difluoro)anilines induced by ZnCl₂ was investigated. The formation of two possibleortho-alkenylated reaction products was observed. The ratio of these isomers depends on the nature of the acid catalyst. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 188–190, January, 1998.     

Selective ortho C−H Cyanoalkylation of (Diacetoxyiodo)arenes through [3,3]‐Sigmatropic Rearrangement

We herein report a robust catalyst‐free cross‐coupling between ArI(OAc)₂ and α‐stannyl nitriles, aided by TMSOTf. The transformation introduces a cyanoalkyl group to the ortho position of ArI(OAc)₂ and simultaneously reduces the aryl iodine(III) to iodide, thus providing α‐(2‐iodoaryl) nitrile as the product. This transformation could be completed within 5 min at ?78 °C and features superb functional‐group tolerance and efficient scalability. DFT calculations indicate that the formation of a ketenimine(aryl)iodonium intermediate and subsequent [3,3]‐sigmatropic rearrangement are involved as key steps.     

The Reaction of o-Benzyne with Vinylacetylene: An Unexplored Way to Produce Naphthalene

The mechanism and kinetics of the reaction of ortho-benzyne with vinylacetylene have been studied by ab initio and density functional CCSD(T)-F12/cc-pVTZ-f12//B3LYP/6-311G(d,p) calculations of the pertinent potential energy surface combined with Rice-Ramsperger-Kassel-Marcus - Master Equation calculations of reaction rate constants at various temperatures and pressures. Under prevailing combustion conditions, the reaction has been shown to predominantly proceed by the biradical acetylenic mechanism initiated by the addition of C₄H₄ to one of the C atoms of the triple bond in ortho-benzyne by the acetylenic end, with a significant contribution of the concerted addition mechanism. Following the initial reaction steps, an extra six-membered ring is produced and the rearrangement of H atoms in this new ring leads to the formation of naphthalene, which can further dissociate to 1- or 2-naphthyl radicals. The o-C₆H₄+C₄H₄ reaction is highly exothermic, by ∼143 kcal/mol to form naphthalene and by 31–32 kcal mol⁻¹ to produce naphthyl radicals plus H, but features relatively high entrance barriers of 9–11 kcal mol⁻¹. Although the reaction is rather slow, much slower than the reaction of phenyl radical with vinylacetylene, it forms naphthalene and 1- and 2-naphthyl radicals directly, with their relative yields controlled by the temperature and pressure, and thus represents a viable source of the naphthalene core under conditions where ortho-benzyne and vinylacetylene are available.     

Ortho effect: The fragmentation of isopropyl 2-hydroxychlorocarbanilates

The mass spectra of isopropyl 2-hydroxychlorocarbanilate indicate a preferential ortho intramolecular rearrangement which yields a chloro 2-benzoxazolinone intermediate ion. A com-parison of the fragmentation of ortho, meta and para hydroxy analogs of isopropyl 3-chlorohydroxy-carbanilate indicates the existence of an ‘ortho effect’ during the fragmentation of isopropyl-chloro 2-hydroxycarbanilates.     

Oxidative cleavage of S-arylmercaptoacetic acids by sodium perborate: Kinetic and correlation study

Kinetics of oxidation of twenty six S-arylmercaptoacetic acids (SAMA) (I) by sodium perborate (PB) have been studied in acid medium. The product of oxidation is the corresponding thiophenol. The rate data of meta-and para-substituted acids have been correlated with DSP equations. While the para-compounds correlate well with σ_I and σ_R° values, the meta-compounds correlate well with σ_I and σ values. The reaction constants are negative and of smaller magnitudes. Further, the ortho-substituted acids show a good correlation with a triparametric equation involving Taft's σ_I and _R° and Charton's steric parameter ν. There is a considerable steric contribution to the total ortho-substituent effect. Based on these observations, mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed. © 1995 John Wiley & Sons, Inc.     

“<Emphasis Type="Italic">ortho</Emphasis>-Effect” in thermal curtius rearrangement of alkylbenzoyl azides into isocyanates: A quantitative interpretation

The reasons for abnormally high reactivity of ortho-alkylbenzoyl azides in thermal Curtius rearrangement were established by the density functional method (PBE/TZ2P approximation). The key factor responsible for the rearrangement rate is the destabilization of the conjugated structure of arylacyl azide through steric effects of the ortho-substituents. Additional intramolecular hydrogen bonding, as in o-hydroxybenzoyl azide molecule, stabilizes the conjugated structure and increases the energy barrier to the reaction. Quantitative interpretation of the “ortho-effect” is given based on the dependence of the reactivity of ortho-alkylbenzoyl azides on the dihedral angle, which characterizes the extent of coplanarity of the acyl azide group and benzene ring. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 7–13, January, 2007.     

C→N Migrations of the ethoxycarbonyl group in reactions of ortho-substituted aryl isocyanates with the 1,3-zwitterion derived from triisopropylphosphine and ethyl 2-cyanoacrylate

The reactions of meta—para-substituted aryl isocyanates with phosphorus-containing 1,3-zwitterions, which proceed with the CN migration of the CO₂Et group to form the corresponding carbamates, were extended to ortho-substituted aryl isocyanates. The influence of the steric and electronic effects of the ortho substituents in the aromatic rings of aryl isocyanates on the ease of this rearrangement is qualitatively considered.     

Effects of silica surface and external magnetic field on photochemical reaction of phenyl esters

Photolysis of phenyl phenylacetate and its derivatives in homogeneous solutions results in photo-Fries rearrangement products, phenols and diphenylethane as well as phenyl benzyl ethers. Photolysis of these esters adsorbed on silica surface leads only to the formation of or/tho-hydroxyphenones and phenyl benzyl ethers. This observation demonstrates that silica surfaces suppress diffusion and rotation of the photogenerated radicals. Application of a weak external magnetic field upon photolysis of these esters adsorbed on silica surface results in no change in the product distribution, suggesting that the photochemical reaction of these esters originates from the excited singlet state. The rate of the formation of the ortho rearrangement product from the geminate radical pairs adsorbed on silica surfaces is estimated to be 2.0 x 10⁸ s^-1.     

Iodane-Guided ortho C−H Allylation

A metal-free C−H allylation strategy is described to access diverse functionalized ortho-allyl-iodoarenes. The method employs hypervalent (diacetoxy)iodoarenes and proceeds through the iodane-guided “iodonio-Claisen” allyl transfer. The use of allylsilanes bearing electron-withdrawing functional groups unlocks the functionalization of a broad range of substrates, including electron-neutral and electron-poor rings. The resulting ortho-allylated iodoarenes are versatile building blocks, with examples of downstream transformation including a concise synthesis of the experimental antimitotic core of Dosabulin. DFT calculations shed additional light on the reaction mechanism, with notable aspects including the aromatic character of the transition-state structure for the [3,3] sigmatropic rearrangement, as well as the highly stereoconvergent nature of the trans-product formation.     

Massenspektrometrische Untersuchung von Amiden. IV—Nachbargruppenbeteiligung Bei der Elektronensto-Ssinduzierten Fragmentierung von O-Nitrobenzoesaurepiperidid

The differences in the electron-impact-induced fragmentation of ortho and para- nitrobenzoylpiperidine are connected with neighbouring group participation of the NO₂ group. New oxygen migration, as well as the formation of stabilised radicals by intramolecular interaction of both functions, are only possible with the ortho compound.     

Phototransformations of 6-X-5-Nitroquinoxalines

Photophysical properties and photochemical activity of 6-X-5-nitroquinoxalines with electron-donor substituents (X = H, CH₃, Cl, OC₂H₅, NH₂) ortho to the nitro group were studied. The quantum yield of the formation of 5-hydroxyquinoxaline from the corresponding nitro derivative depends on the nature of the substituent and irradiation conditions. Phototransformations can go through nitro-nitrite rearrangement with the participation of two alternative T(n*) levels, depending on the size and electronic effects of the substituent. The latter factor is largely determined by the population on excitation of different charge-transfer states involving the nitro group.     

Formation of basic compounds during the indole cyclization of ketone phenylhydrazones

On the basis of previous occasional findings, the Fischer indole cyclization of ten ketone phenylhydrazones containing moieties of increasing bulkiness was investigated in order to isolate eventual side products. In the cases of the three 2-, 3- and 4-acetylpyridine phenylhydrazones the corresponding 2-pyridylindoles were the sole compounds so far isolated. In all the remaining cases, beside the indoles a mixture of basic compounds was obtained. In all cases aniline and a 2-substituted (2-methyl or 2-phenyl)benzimidazole were formed, the last resulting through an apparent ortho-semidinic rearrangements of phenylhydrazones. Starting from methyl isopropyl ketone phenylhydrazone a compound of formula C₁₁H₁₅NO was also isolated, to which the structure of 3-(4-aminophenyl)-3-methylbutanone was assigned on the basis of ir, nmr spectra and of the chemical reactivity. The formation of this compound seems related to a para-benzidine-like rearrangement of phenyl hydrazone.     

Characterization of multiple fragmentation pathways initiated by collision‐induced dissociation of multifunctional anions formed by deprotonation of 2‐nitrobenzenesulfonylglycine

The correlation of anion structure with the fragmentation behavior of deprotonated nitrobenzenesulfonylamino acids was investigated using tandem mass spectrometry, isotopic labeling and computational methods. Four distinct fragmentation pathways resulting from the collision‐induced dissociation (CID) of deprotonated 2‐nitrobenzenesulfonylglycine (NsGly) were characterized. The unusual loss of the aryl nitro substituent as HONO was the lowest energy process. Subsequent successive losses of CO, HCN and SO₂ indicated that an ortho cyclization reaction had accompanied loss of HONO. Other pathways involving rearrangement of the ionized sulfonamide group, dual bond cleavage and intramolecular nucleophilic displacement were proposed to account for the formation of phenoxide, arylsulfinate and arylsulfonamide product ions at higher collision energies. The four distinct fragmentation pathways were consistent with precursor–product relationships established by CID experiments, isotopic labeling results and the formation of analogous product ions from 2,4‐dinitrobenzenesulfonylglycine and the Ns derivatives of alanine and 2‐aminoisobutyric acid. The computations confirmed a low barrier for ortho cyclization with loss of HONO and feasible energetics for each reaction step in the four pathways. Computations also indicated that three of the fragmentation pathways started from NsGly ionized at the carboxyl group. Overall, the pathways identified for the fragmentation of the NsGly anion differed from processes reported for anions containing a single functional group, demonstrating the importance of functional group interactions in the fragmentation pathways of multifunctional anions. Copyright © 2014 John Wiley & Sons, Ltd.