Substituent and solvent effects

The gas phase acid/base properties of molecules have been subject to equilibrium or bracketing measurements employing mass spectrometric techniques like ion cyclotron resonance (ICR) [4], Fourier transform ion cyclotron resonance (FT-ICR) [5,6], Flowing afterglow (FA) and Selected ion flow tube (SIFT) [7], and high pressure mass spectrometry (HPMS) [8]. Proton transfer between neutral molecules are then investigated by measurements of reactions 

It has been demonstrated that it is possible to determine reliable relative basicities by employing the kinetic method. By this method, a proton bonded dimer is caused to dissociate, and the difference in basicity of the constituent monomers is derived from the ratio of ionic products of the two competing dissociation channels [9]  

This technique is especially valuable in cases where equilibrium measurement is hampered due to low volatility (peptides, zwitterions, salts etc.). Gas phase acidity (GA) and basicity (GB), and proton affinity (PA) are defined in the absolute sense through the following definitions  

When reliable data are at hand, it is possible to compare gas phase and solution properties. For the anions of the first-row hydrides the following order of 

The gas phase basicity order of the neutral molecules NH3 H20 HF is the same as that found in aqueous solution. Also in this case the solvation energies are substantial, both for acid and base. For this reason it is difficult to know whether the solution behaviour reflects the intrinsic electronic properties of the molecule, or if the sum of solvent/solute interactions partially cancel out in a pattern which resembles the acidity and basicity orders. 

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Saito, R., Hirano, T., Niwa, H., and Ohashi, M. (1997). Solvent and substituent effects on the fluorescent properties of coelenteramide analogues. J. Chem. Soc., Perkin Trans. 2, pp. 1711-1716. 

Carbocation-carbanion zwitterionic intermediates were proposed for the thermal cleavage of several cyclic compounds. In most of these reactions the ionically dissociating bond belongs to one of four strained ring systems, i.e. cyclopropane (13), cyclobutane (14), cyclobutene (15) or norbornadiene (16). The mechanism is distinguished from the formation of a diradical intermediate through homolysis in terms of solvent and substituent effects... 

Information on the mechanism is mainly obtained from kinetic solvent and substituent effects, i.e. from p- and m-values, as discussed below. These coefficients are therefore a composite of p- and m-values for CTC and ionization steps as shown in (9). Obviously, neither Pctc nor mCTC is available... 

KSIEs for the reaction of aromatic olefins, 1,1-diphenylethylene and a-methylstyrene (Table 21) are significantly smaller they can be related to transition states earlier than those in the aliphatic series. Unfortunately, for the reactions of highly reactive aromatic olefins or enol ethers, whose low sensitivity to solvent and substituent effects indicates very early transition states, there are not enough KSIE data to confirm this conclusion. 

With a few exceptions simple 1,2,3-oxadiazoles (1) are not isolable because they are less stable than their open tautomers (2) (Equation (1)). The sterically protected 1,2,3-oxadiazole (3) is the only known oxadiazole bearing alkyl substituents. It exists in the cyclic form in the crystalline state but as the diazoketone in chloroform solution <80TH 403-01 >. 1,2,3-Benzoxadiazolehas been detected in a matrix at 15 K <84AG(E)509> this and some substituted 1,2,3-benzoxadiazoles have been shown to exist in equilibrium with their open-chain tautomers <91JST(247)135>. The position of the equilibrium is strongly dependent upon solvent and substituent effects the most stable of the... 

Abstract The main computational studies on the formation of (3-lactams through [2+2] cycloadditions published during 1992-2008 are reported with special emphasis on the mechanistic and selectivity aspects of these reactions. Disconnection of the N1-C2 and C3-C4 bonds of the azetidin-2-one ring leads to the reaction between ketenes and imines. Computational and experimental results point to a stepwise mechanism for this reaction. The first step consists of a nucleophilic attack of the iminic nitrogen on the sp-hybridized carbon atom of the ketene. The zwitterionic intermediate thus formed yields the corresponding (3-1 actant by means of a four-electron conrotatoty electrocyclization. The steroecontrol and the periselectivity of the reaction support this two-step mechanism. The [2+2] cycloaddition between isocyanates and alkenes takes place via a concerted (but asynchronous) mechanism that can be interpreted in terms of a [n2s + (n2s + n2s)] interaction between both reactants. Both the regio and the stereochemistry observed are compatible with this computational model. However, the combination of solvent and substituent effects can result in a stepwise mechanism. 

Detailed mechanisms of intramolecular rearrangement reactions have been difficult to determine. Classical rate measurements seldom lead to unambiguous mechanistic predictions. Generally only after extensive examination of concentration, solvent, and substituent effects on the reaction rate can a general mechanistic class be proposed for example, intra vs intermolecular or bond rupture of a bidentate chelate vs non-bond rupture twist pathways. Indeed, only two examples of slow complexes are known where detailed rate comparisons for geometrical and optical iso-merizations were made and used to eliminate several mechanisms however, a single most probable pathway was not demonstrated in either case.12,13 Only with DNMR can detailed environmental site interchanges be directly observed and with this in-... 

Sharshira, E.M., Okamura, M., Hasegawa, E., and Horaguchi, T. (1997) Photocyclization reactions. Part 6 [1]. Solvent and substituent effects in the synthesis of dihydrobenzofuranols using photocyclization of 2-alkoxybenzo-phenones and ethyl 2-benzoylpheno-xyacetates. Journal of Heterocyclic Chemistry, 34, 861-869. 

Hayes, W.P. and Timmons C.J., Solvent and substituent effects on the mEn absorption bands of some ketones. Spectrochim. Acta (1965) 21 529-541. 

The discovery of Brauman and Blair in 1968 [34] that the acidities of aliphatic alcohols are completely reversed on going from bulk solution to the gas phase was a landmark in the interpretation of solvent and substituent effects on acid/base equihbria. The gas-phase acidity of alcohols increases in the following order [34, 125, 126] ... 

For this reaction, the rate was found to vary by a factor of 34 in going from the least polar ( -tetradecane) to the most polar solvent (phenol), and by a factor of 102 in going from the gas phase to the most polar solvent [153]. The small solvent and substituent effects observed suggest that a slightly dipolar activated complex must be formed during the Claisen rearrangement of this allyl aryl ether [153]. 

In addition to the temperature, solvent, and substituent effects, a preference for either the arene oxide or oxepin form may be achieved by localization of one double bond as part of an aromatic ring system. Thus the reluctance to form a cyclobutadiene ring causes 10 to exist preponderantly as its oxide form. Naphthalene 1,2-oxide 11 is the simplest arene-oxide member in the polycyclic aromatic hydrocarbon (PAH) series and exists exclusively in that tautomeric form. In contrast, naphthalene 2,3-oxide exists exclusively as the oxepin form 12 since the C4-CS bond in the oxepin ring forms part of an aromatic ring. ... 

Salt, solvent, and substituent effects in the alkaline hydrolysis (and alkoxide-promoted decomposition) of phosphonium compounds have been reviewed. The rate of alkaline hydrolysis of tetraphenylphosphonium chloride in DMSO-water mixtures increases by as much as 10 -fold as the DMSO content is increased, due to desolvation of the reactant ions. ... 

These marked metal ion effects (7), in conjunction with well known solvent and substituent effects, suggest that an ionic mechanism is operative in the metal ion catalyzed Wittig reaction (7Z>). An ionic mechanism for the Wittig half-reaction of benzylidenetriphenylphosphorane with aldehydes can be envisioned as shown in Figure 1. 

Lithoxoidou, A.T., and Bakalbassis, E.G., PCM study of the solvent and substituent effects on the conformers, intramolecular hydrogen bonds and bond dissociation enthalpies of 2-substituted phenols, J. Phys. Chem. A, 109, 366-377 (2005). 

Solvent and Substituent Effects in the Anionic Polymerization of o ,Q -Disubstituted j3-Propiolactones... 

Solvent and substituent effects in the anionic polymerization of a-ethyl-a-ri-butyl-6-proplolactone, EBPL, were Investigated in dimethyl sulfoxide and in N-methylpyrrolidone. In dimethyl sulfoxide,... 

LENZ ET AL. Solvent and Substituent Effects in Anionic Polymerization... 

Saito R, Hirano T, Niwa H, Ohashi M. Solvent and substituent effect on the fluorescent propaties of coelentaamide analogues. J Chem Soc Pa-kin Trans 21997 1711-6. Strya L. Excited state proton-transfa reactions. A deuterium isotope effert on fluorescence. J Am Chem Soc 1966 88 5708-12. 

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