Inter- and intramolecular mechanisms for chlorine rearrangements in trimethyl-substituted N-chlorohydantoins

The antimicrobial compounds 1-chloro-3,5,5-trimethylhydantoin and 3-chloro-1,5,5-trimethylhydantoin (1 and 2, respectively) have been synthesized and examined via a joint experimental and computational study. The measured rate of loss of oxidative chlorine in the absence and presence of exposure to UVA irradiation determined 2 to be less stable than 1. An interesting migration reaction was observed during UVA irradiation that featured the production of chlorine rearrangement and dechlorinated compounds. Two novel hydrogen atom transfer reaction (HATR) mechanisms have been proposed: (1) an intramolecular process in which a hydrogen atom undergoes a series of sigmatropic shifts, and (2) an intermolecular pathway in which a radical abstracts a hydrogen atom from a neighboring molecule. Density functional theory (DFT) calculations at the UB3LYP/6-311G++(2d,p) theory level have been employed to elucidate the preferred reaction pathway. Both proposed HATR mechanisms predicted 2 to possess a lower free energy of activation, ΔG(?), relative to 1 in accordance with the experimental stability measurements. However, the intermolecular route had an overall lower absolute ΔG(?) and was more consistent with measured product ratios in solution. The intermolecular reaction pathway, unlike the intramolecular route, also predicted the lack of formation of a migration product featuring a Cl covalently bonded to a methylene group at the 5-position of the hydantoin moiety, which was verified by NMR experiments.     

Palladium-catalyzed intramolecular alpha-arylation of alpha-amino acid esters.

The Pd-catalyzed intramolecular alpha-arylation of alpha-amino acid esters is described. Starting from readily available amino acids, the synthesis of a variety of isoindolines and tetrahydroisoquinoline carboxylic acid esters has been accomplished. Additionally, fused tricyclic systems can be efficiently prepared from cyclic amino acid esters. Reaction conditions have been found that allow the use of tert-butyl ester and N-(benzyloxycarbonyl) protecting groups.     

General base and general acid catalyzed intramolecular aminolysis of esters. Cyclization of esters of 2-aminomethylbenzoic acid to phthalimidine

Plots of log k(0) vs pH for the cyclization of trifluoroethyl and phenyl 2-aminomethylbenzoate to phthalimidine at 30 degrees C in H(2)O are linear with slopes of 1.0 at pH >3. The values of the second-order rate constants k(OH) for apparent OH(-) catalysis in the cyclization reactions are 1.7 x 10(5) and 5.7 x 10(7) M(-)(1) s(-)(1), respectively. These rate constants are 10(5)- and 10(7)-fold greater than for alkaline hydrolysis of trifluoroethyl and phenyl benzoate. The k(OH) for cyclization of the methyl ester is 7.2 x 10(3) M(-)(1) s(-)(1). Bimolecular general base catalysis occurs in the intramolecular nucleophilic reactions of the neutral species. The value of the Bronsted coefficient beta for the trifluoroethyl ester is 0.7. The rate-limiting step in the general base catalyzed reaction involves proton transfer in concert with leaving group departure. The mechanism involving rate-determining proton transfer exemplified by the methyl ester in this series (beta = 1.0) can then be considered a limiting case of the concerted mechanism. General acid catalysis of the neutral species reaction or a kinetic equivalent also occurs when the leaving group is good (pK(a) 相似文献   

Inter- and intramolecular excited state proton transfer in 2-hydroxy-9H-carzole-1-carboxylic acid

Absorption, fluorescence and fluorescence excitation spectroscopy and single photon counting time dependence spectrofluorimetry have been used to study the inter- and intramolecular excited state proton transfer (ESIPT) reactions in 2-hydroxy-9H-carbazole-1-carboxylic acid (2-HCA). Except in cyclohexane and water (pH 5) dual fluorescence is observed in rest of the solvents used. Normal Stokes shifted band seems to originate from 2-HCA-1-c and tautomer emission band from the tautomer formed by ESIPT in 2-HCA-1-c followed by structural reorganization. Both these emission band systems originate from the same ground state species. AM1 and CNDO/S-CI calculations have been carried out to establish the identity of the species. Different prototropic equilibria have been determined and discussed.     

Inter- and intramolecular stereoselective protonation of enols(1,2)

Kinetic control of the stereoselectivity of protonation of enolates and other delocalized species commonly affords the less stable diastereomer as a consequence of the considerable exothermicity and resulting sp(2) transition-state hybridization of the alpha-carbon. Protonation then is from the less hindered face of the enolate. The present study is aimed at reversing this phenomenon by intramolecular delivery of the proton. The approach employed required the synthesis of two enolate precursors, one with a 2-pyridyl group strategically close to the alpha-carbon and the other with a phenyl group in the same location. The synthesis required 15 steps and involved new methodology. Intramolecular proton transfer, reversing the usual stereoselectivity, was successful. The selectivity proved to depend on several factors including the exo versus endo configuration of the diastereomer reacting, the proton donor employed, and the concentration of the proton donor. A kinetic analysis permitted the determination of the relative reaction orders of the protonation on the two faces of the enolate.     

The use of esters of dichloromaleic acid in intramolecular diels alder reactions

Intramolecular cyclisation of acyclic triene esters derived from dichloromaleic anhydride affords bicyclic lactones, which by dechlorodecarboxylation, dechlorination or dehydrochlorination are readily elaborated to give novel unsaturated lactones.     

Inter- and intramolecular hydroacylation of alkenes employing a bifunctional catalyst system

Based on a conceptually innovative bifunctional P,N ligand, an efficient protocol for the rhodium-catalyzed inter- and intramolecular hydroacylation of alkenes has been developed.     

Gas-phase acid-base properties of melamine and cyanuric acid

The thermochemical properties of melamine and cyanuric acid were characterized using mass spectrometry measurements along with computational studies. A triple-quadrupole mass spectrometer was employed with the application of the extended Cooks kinetic method. The proton affinity (PA), gas-phase basicity (GB), and protonation entropy (Δ_pS) of melamine were determined to be 226.2 ± 2.0 kcal/mol, 218.4 ± 2.0 kcal/mol, and 26.2 ± 2.0 cal/mol K, respectively. The deprotonation enthalpy (Δ_acidH), gas-phase acidity (Δ_acidG), and deprotonation entropy (Δ_acidS) of cyanuric acid were determined to be 330.7 ± 2.0 kcal/mol, 322.9 ± 2.0 kcal/mol, and 26.1 ± 2.0 cal/mol K, respectively. The geometries and energetics of melamine, cyanuric acid, and related ionic species were calculated at the B3LYP/6-31+G(d) level of theory. The computationally predicted proton affinity of melamine (225.9 kcal/mol) and gas-phase deprotonation enthalpy of cyanuric acid (328.4 kcal/mol) agree well with the experimental results. Melamine is best represented as the imide-like triazine-triamine form and the triazine nitrogen is more basic than the amino group nitrogen. Cyanuric acid is best represented as the keto-like tautomer and the N-H group is the most probable proton donor.     

Substituent effect and rearrangements in the electron-impact spectra of long chain esters of m-and p-methoxybenzoic acid

The mass spectra of eighteen n-alkyl estars of p-methoxybenzoic acid are examined. Few differences exist in the spectra of the corresponding para and meta isomers. We describe a new rearrangement, loss of OH from the molecular ion, whichis observed only in the para substituted isomkers. Oxygen-18 labeling indicates that the oxygen lost in the [M? OH]+ ion derives from the carbonyl. No indication is found of hydrogen abstration from the chain by the methoxy group competing withthe benzoate ester rearrangement. We find a substituent effect on that rearrangement, with electron-donating groups decreasing the values of [ArCO₂H₂]⁺/[ArCO₂H]⁺· ion ratios. this ratio decreases as the ester chain length increases.     

Bismuth-catalyzed intramolecular carbo-oxycarbonylation of 3-alkynyl esters

Borderline metal complexes, especially Bi(OTf)3, efficiently catalyze the carbo-oxycarbonylation of alkynyl esters to form multisubstituted lactones in moderate to high yields.     

Determinants of cyanuric acid and melamine assembly in water

While the recognition of cyanuric acid (CA) by melamine (M) and their derivatives has been known to occur in both water and organic solvents for some time, analysis of CA/M assembly in water has not been reported (Ranganathan, A.; Pedireddi, V. R.; Rao, C. N. R. J. Am. Chem. Soc.1999, 121, 1752-1753; Mathias, J. P.; Simanek, E. E.; Seto, C. T.; Whitesides, G. M. Macromol. Symp.1994, 77, 157-166; Zerkowski, J. A.; MacDonald, J. C.; Seto, C. T.; Wierda, D. A.; Whitesides, G. M. J. Am. Chem. Soc.1994, 116, 2382-2391; Mathias, J. P.; Seto, C. T.; Whitesides, G. M. Polym. Prepr.1993, 34, 92-93; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1993, 115, 905-916; Zerkowski, J. A.; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1992, 114, 5473-5475; Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.1990, 112, 6409-6411; Wang, Y.; Wei, B.; Wang, Q. J. Chem. Cryst.1990, 20, 79-84; ten Cate, M. G. J.; Huskens, J.; Crego-Calama, M.; Reinhoudt, D. N. Chem.-Eur. J.2004, 10, 3632-3639). We have examined assembly of CA/M, as well as assembly of soluble trivalent CA and M derivatives (TCA/TM), in aqueous solvent, using a combination of solution phase NMR, isothermal titration and differential scanning calorimetry (ITC/DSC), cryo-transmission electron microscopy (cryo-TEM), and synthetic chemistry. While the parent heterocycles coprecipitate in water, the trivalent system displays more controlled and cooperative assembly that occurs at lower concentrations than the parent and yields a stable nanoparticle suspension. The assembly of both parent and trivalent systems is rigorously 1:1 and proceeds as an exothermic, proton-transfer coupled process in neutral pH water. Though CA and M are considered canonical hydrogen-bonding motifs in organic solvents, we find that their assembly in water is driven in large part by enthalpically favorable surface-area burial, similar to what is observed with nucleic acid recognition. There are currently few synthetic systems capable of robust molecular recognition in water that do not rely on native recognition motifs, possibly due to an incomplete understanding of recognition processes in water. This study establishes a detailed conceptual framework for considering CA/M heterocycle recognition in water which enables the future design of molecular recognition systems that function in water.     

Configurational stability of oxymethyllithiums as intermediates in intramolecular rearrangements

Several homochiral oxymethyllithiums, chiral by virtue of the hydrogen isotopes protium and deuterium, were prepared. They were tested for their microscopic configurational stability in intramolecular isomerizations, such as the silyl- and germyl-[1,2]-retro-Brook and the sigmatropic[2,3]-Wittig rearrangement. The influence of temperature, solvent, and migrating group on the stability of the intermediate carbanions was studied. Furthermore, the stereochemical course of these rearrangements was elucidated, resulting in highly enantioenriched alcohols (90-97% ee; ee=enantiomeric excess) up to temperatures of 0 degrees C.     

Mass spectral rearrangements in benzylidene hippuric esters

The mass spectra of a series of hippuric esters have been determined. A variety of novel rearrangements induced by the presence of a formed benzyl carbonium ion has been rationalized with the aid of high resolution measurements and isotopic and substituent labeling. An eight centered rearrangement is proposed for the observed transfer of oxygen from a nitro group to a double bond.     

Inter- and intramolecular isocarbon couplings of cobalt-complexed propargyl radicals: challenging the consensus

Intermolecular coupling reactions of Co₂(CO)₆-complexed, γ-ethyl propargyl radicals occurred with higher dl-diastereoselectivity than intramolecular cyclizations of isocarbon analogues (de_inter−de_intra≤52%). The observed phenomenon was interpreted in terms of a tandem action of two main determinants—sterics and CH/π coordination—with the latter being enabled by the methoxy groups located on the periphery of the aromatic nuclei (4-, 3,4-, 3,4,5-).