Nucleophilic substitution reaction of benzyl benzenesulfonates with anilines in methanol-acetonitrile mixtures. Part 3

Kinetic studies on the nucleophilic substitution reaction of para-nitrobenzyl benzenesulfonates with anilines in methanol-acetonitrile mixtures are reported. It was found that the reaction proceeds via a dissociative S_N2 mechanism with a more product -like transition state compared to that for substrate with a less electron attracting substituent. A stronger electron withdrawing substituent in the benzyl moiety and in the leaving group is shown to enhance both bond making and bond breaking but the enhancement of bond making was found to be greater than that of bond breaking.     

Theoretical study on the substituent effect of a Wittig reaction

The substituent effects of F, H and methyl (Me) in replacement of phenyl (Ph) groups bonding with the ylide phosphorus in Wittig reactions have been examined theoretically by performing ab intio calculations. It is shown that the energy barrier for the Wittig reaction with F as the substituent is much higher than that with H, Me and Ph. The Wittig reaction is found to be more favorable with the substituent in the order F<H<Ph<Me. The reactions are found to proceed through two transition states: the formation and the decomposition of oxaphosphetane. We conclude that only the model of the Wittig reaction in which Ph is simplified to Me can reasonably describe the real Wittig reaction. Received: 7 August 2001 / Accepted: 25 October 2001 / Published online: 22 March 2002     

N-Tosylaziridine, a new substrate for chemical fixation of carbon dioxide via ring expansion reaction under atmospheric pressure

N-Tosylaziridine was found to be a useful substrate for cycloaddition reaction with carbon dioxide. The reaction was successfully catalyzed by lithium bromide under atmospheric pressure to give the corresponding five-membered cyclic urethane, N-tosyl-1,3-oxazolidin-2-one, selectively. It was found that electron-donating nature of the substituent at 2-position of N-tosylaziridine accelerated the reaction, and this tendency allowed us to estimate the reaction mechanism.     

Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

The first examples of a Type 3 ring opening reaction of cyclopropanated oxabenzonorbornadiene (CPOBD) were found to occur using alcohol nucleophiles under acid catalyzed conditions, yielding seven-membered rings via ring expansion. Optimization of the reaction determined the ideal conditions to be 10?mol% pTsOH at 40?°C using excess alcohol nucleophile as the solvent. The scope of the reaction investigated diverse alcohol nucleophiles and bridgehead substituents on the CPOBD; in both cases the steric properties of the substituent was found in influence the yield of the reaction. Alternative Type 3 products were observed when the bridgehead substituent was an ethyl or hydroxymethyl group and limited examples of Type 3 products were formed using a palladium catalyst with alcohol nucleophiles. Mechanisms have been proposed for the formation of the Type 3 product as well as the alternative Type 3 products.     

Investigation of the catalytic activity of a Pd/biphenyl-based phosphine system in the Ullmann homocoupling of aryl bromides

We described Ullmann homocoupling promoted by a Pd/biphenyl-based phosphine system using DMF as solvent. Using Hammett equation it is found that the rate determining step of the reaction depends on the electronic nature of substituents of aryl bromides. Increase the rate of reaction with decreasing the electron donating of the substituent from NH₂ to H suggesting an oxidative addition step as the rate determining step. Decrease the rate of reaction with increasing the electron-withdrawing ability of the substituent from H to NO₂ indicating a reductive elimination step as the rate determining step.     

Enthalpic and entropic contributions to substituent effects for the ionization of meta- and para-nitrobenzoic acids in water-dimethylsulphoxide mixtures at 25°C

Enthalpic and entropic contributions to substituent effects for the ionization of m-and p-nitrobenzoic acids are examined, ranging from pure water to 0.8 mole fraction DMSO. The effect of the medium on the substituent and reaction constants is explained in terms of solute—solvent interactions. No structure-breaking effect was found.     

Racemization of sulfinic esters with trichloroacetic anhydride

Both alkane- and arene-sulfinates undergo racemization and oxygen exchange reaction with trich-loroacetic anhydride. The rate of racemization of (?)menthyl (?)p-toluenesulfinate was found to be twice that of oxygen exchange, suggesting the reaction involves a Walden inversion. When reaction was carried out in benzene, the rate of racemization was found to be first order with respect to both sulfinic ester and trichloroacetic anhydride. The substituent effect is large (p = ?1.53) suggesting that the initial acylation is the rate-determining step. The rate of racemization was found to be retarded by the addition of perhaloacetic acid while very small catalytic effect of mercuric chloride was observed.     

Platinum oxide catalyzed hydrosilylation of unsymmetrical internal aryl alkynes under ortho-substituent regiocontrol

[chemical reaction: see text]. PtO2- and H2PtCl6-catalyzed hydrosilylation of internal aryl alkynes having a para or an ortho substituent with triethylsilane are discussed and compared. The regioselectivity of the H-Si bond addition was found to be controlled by the ortho substituent rather than the nature of the platinum catalyst. Arylalkynes with an ortho substituent, regardless of its electronic nature, directed the silyl substituent mainly to the alpha-position. PtO2 proved to be a versatile and powerful catalyst compared to H2PtCl6 since it prevents the alkyne reduction.     

Synthesis of 5-hydroxyquinolines

A series of 5-hydroxyquinolines has been prepared via the Skraup reaction. Several regioisomers were made either by selective displacement of a leaving group or by using a bromo substituent as a blocking group. The bromo group was found to be an excellent blocking group due to its stability during the Skraup reaction and easy removal thereafter. Halides at the 5-position of quinoline were found to be much more reactive than those at the 7- and 8-positions. Finally, we have also found a unique method to reduce the pyridyl ring on quinolines, leaving a halogen substituent untouched.     

Spectrophotometric study of the reaction between cobalt(II)-dipeptide complexes and molecular oxygen

Summary The influence of pH and ligand structure on the reaction of cobalt(II) complexes with various dipeptides and molecular oxygen was examined. The minimum pH value required for the formation of dioxygen adducts was found to be about 6.5. This value should be related to amidic deprotonation of dipeptides, which seems to occur in the examined systems at particularly low values. The location and steric hindrance of the side chains of the dipeptides have a strong influence on the reaction rate. The presence of a substituent group on the N-terminal amino acid promotes oxygen coordination, while, when the substituent group is on the C-terminal residual, a decrease of reaction rate is observed.A stabilizing effect of the aromatic ring on the dioxygen adducts is found only when the substituent is in the C-terminal position, and seems to be independent of the presence of additional coordinating groups.Some information regarding the mechanism of the irreversible decomposition of the cobalt(II) complexes has been obtained by studying the effect of pH and ligand structure on the reaction rate.Work supported by National Research Council of Italy.     

A Direct Approach to the cis-1-Octalone System. 2-Carbomethoxy-2-Cyclohexenone as a Dienophile

Under stannic chloride catalysis, 2-carbo-methoxy-2-cyclohexenone (1) was found to undergo Diels-Alder reaction with a variety of dienes to give directly the cis-1-octalone system possessing a functionalized substituent at the angular position.     

Baylis‐Hillman Reaction of Arylaldehydes with Phenyl Vinyl Ketone,Phenyl Acrylate,and Phenyl Thioacrylate

In the Baylis‐Hillman reaction of aryl aldehydes with phenyl vinyl ketone, we found that the diadduct 4 was exclusively formed, and that the yield of 4 can reach 80% with increasing amounts of phenyl vinyl ketone. But, for phenyl acrylate and phenyl thioacrylate, only the normal Baylis‐Hillman adduct was obtained. The substituent effects were also examined, and a plausible reaction mechanism was proposed for the formation of 4 .     

Mass spectrometric detection of the Gibbs reaction for phenol analysis

This paper describes a new method for detecting phenols, by reaction with Gibbs reagent to form indophenols, followed by mass spectrometric detection. Unlike the standard Gibbs reaction, which uses a colorometric approach, the use of mass spectrometry allows for simultaneous detection of differently substituted phenols. The procedure is demonstrated to work for a large variety of phenols without para‐substitution. With para‐substituted phenols, Gibbs products are still often observed, but the specific product depends on the substituent. For para groups with high electronegativity, such as methoxy or halogens, the reaction proceeds by displacement of the substituent. For groups with lower electronegativity, such as amino or alkyl groups, Gibbs products are observed that retain the substituent, indicating that the reaction occurs at the ortho or meta position. In mixtures of phenols, the relative intensities of the Gibbs products are proportional to the relative concentrations, and concentrations as low as 1 μmol/L can be detected. The method is applied to the qualitative analysis of commercial liquid smoke, and it is found that hickory and mesquite flavors have significantly different phenolic composition.     

Effect of meso-substituents on the osmium tetraoxide reaction and pinacol-pinacolone rearrangement of the corresponding vic-dihydroxyporphyrins

To investigate the effects of electron-donating and electron-withdrawing substituents upon the reaction of porphyrins with osmium tetraoxide, and the pinacol-pinacolone rearrangement of the resulting diols, a series of meso-substituted porphyrins were prepared by total synthesis. Porphyrins with electron-donating substitutents at the meso-positions gave vic-dihydroxychlorins in which the adjacent pyrrole subunit was predominantly oxidized. No such selectivity was observed in a porphyrin containing a methoxycarbonyl as the electron-withdrawing group, whereas a formyl substituent again resulted in oxidation at the pyrrole unit adjacent to the meso-substituent. Under pinacol-pinacolone conditions, vic-dihydroxy chlorins containing 4-methoxyphenyl or 3,5-dimethoxyphenyl groups at the meso-position showed preferential migration of the ethyl group over the methyl group to give 8-ketochlorins, whereas the diol with an n-heptyl substituent under similar reaction conditions gave both 7- and 8-ketochlorins. In contrast, the diol containing a meso-formyl substituent produced the corresponding 7-ketochlorin exclusively. These results indicate that it is not possible to predict the reactivity of meso-substituted porphyrins in the osmium tetraoxide reaction nor the general substituent migratory aptitudes in the pinacol-pinacolone rearrangement based on simple electronic arguments, most likely because many parameters (e.g., meso-beta-pyrrolic steric crowding and long-range electronic effects) ultimately determine the reactivity. The structural assignments of the porphyrin diols and the keto-analogues were confirmed by extensive (1)H NMR studies; some of the dihydroxychlorins and ketochlorins were found to display unusual features in their (1)H NMR spectra.     

Synthesis and Phosphorylation of 2- and 3-Halomethyl Derivatives of Functionalized 2-tert-Butylfurans

2-Halomethyl derivatives of 3-functionalized 5-tert-butylfurans are phosphorylated underconditions of the Michaelis-Becker, Arbuzov reactions similarly to other halomethylfurans. No effectof the tert-butyl substituent on the yield of the reaction products was found in this case. Contrary to that, the2-methoxymethyl derivative of 3-chloromethyl-5-tert-butylfuran proved to be more thermostable than its analog containing no tert-butyl substituent. As a result, the yield of phosphonate in the Michaelis-Becker reaction under similar conditions increases 2.5 times. The observed stabilization of the furan ring is explained by shielding of its oxygen atom by the tert-butyl group.     

Reaction of metal exchange of cadmium 5,10,15,20-tetraphenylporphyrinate and its β-bromo derivative with zinc acetate in dimethylformamide

Metal exchange of cadmium 5,10,15,20-tetraphenylporphyrinate (CdTPP) and cadmium 2-bromo-5,10,15,20-tetraphenylporphyrinate (CdTPPBr) with zinc acetate in dimethylformamide was spectrophotometrically examined. The kinetic parameters of the metal exchange reaction were determined. A possible stoichiometric mechanism of the reaction was suggested. The effect of the bromo substituent in β-position of the pyrrole in the cadmium tetraphenylporphyrinate on the metal exchange reaction with Zn(OAc)₂ in DMF was found.     

Preparation of novel 1,2,4-thiadiazoles by cyclization with 4-methylbenzenesulfonyl cyanide (tosyl cyanide)

The preparation of 1,2,4-thiadiazoles with a di-tert-butylphenol substituent at the thiadiazole 3-position is described. A thermally generated nitrile sulfide was reacted with tosyl cyanide in a 1,3-dipolar cyclization reaction to provide a thiadiazole intermediate containing a labile 5-tosyl substituent.     

Hammett correlations in the chemistry of 3-phenylpropyl radicals

The energetics and kinetics of the reaction of variously substituted benzyl radicals with a model alkene were calculated at the G3(MP2)-RAD//B3-LYP/6-31G(d) level of theory to determine whether such reactions are amenable to Hammett analysis. The reactions were studied both in the gas phase and in toluene solution in the temperature range 298-353 K; calculations include 1D-hindered rotor corrections for low frequency torsional modes, and the solvation energies were calculated using COSMO-RS at the BP/TZP level of theory. The addition reaction was found to be dominated by radical stabilization effects, but under circumstances where olefin substituent effects were decoupled from aryl substituent effects, a modest polar effect comes into play, which is enhanced by solvation. Reasonable correlations with empirical substituent parameters such as Hammett σ and σ(?) are observed for the enthalpy of activation, but additional entropic factors act to decrease the degree of correlation with respect to free energies and rate coefficients, confirming hypotheses from earlier experimental work. Substituent effects on the reverse β-fragmentation reaction, and potential cyclization of the 3-phenylpropyl radicals formed by addition are also discussed.     

Interaction of dimethyl carbonate with anilines in the presence of potassium methylate: Kinetics and the role of the base

The kinetic patterns of the reaction between dimethyl carbonate and anilines in the presence of a potassium methylate as a catalyst were studied. The mechanism of aminolysis was clarified, which includes the detachment of the proton from the amino group of aniline and the subsequent attack of the resulting anion on the carbonyl group of dimethyl carbonate. It is shown that when the reaction occurs in the dimethyl carbonate-methanol 3:1 system, the process can be described as an irreversible first-order reaction in the aniline though the target reaction is complicated by side interaction between potassium methylate and dimethyl carbonate. The rate constants of the target reaction with substituted anilines and of the side reaction in the temperature range of 70-90°C were determined. It is shown that the influence of the substituent on the reaction rate is described by the Hammett equation, with the constant of the reaction series being positive and the best correlation being achieved for σ-scale. The results obtained are consistent with the proposed mechanism of the reaction and are explained by the facilitation of the aniline deprotonation with increasing acceptor properties of the substituent. Effective activation energies for the reaction of various anilines with dimethyl carbonate are found.