Steric effects derivatives

Jay Kochi In principle, yes. However, the problem is quite a bit more complicated than that encountered with phosphines, in which steric effects derive from a coordination to metal with minimal changes in configuration, e.g.,... 

The adsorptive separation is achieved by one of the three mechanisms steric, kinetic, or equilibrium effect. The steric effect derives from the molecular sieving property of zeolites. In this case only small and properly shaped molecules can diffuse into the adsorbent, whereas other molecules are totally excluded. Kinetic separation is achieved by virtue of the differences in diffusion rates of different molecules. A large majority of processes operate through the equilibrium adsorption of mixture and hence are called equilibrium separation processes. 

The solubility of a compound is thus affected by many factors the state of the solute, the relative aromatic and aliphatic degree of the molecules, the size and shape of the molecules, the polarity of the molecule, steric effects, and the ability of some groups to participate in hydrogen bonding. In order to predict solubility accurately, all these factors correlated with solubility should be represented numerically by descriptors derived from the structure of the molecule or from experimental observations. 

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

Auto-association of A-4-thiazoline-2-thione and 4-alkyl derivatives has been deduced from infrared spectra of diluted solutions in carbon tetrachloride (58. 77). Results are interpretated (77) in terms of an equilibrium between monomer and cyclic dimer. The association constants are strongly dependent on the electronic and steric effects of the alkyl substituents in the 4- and 5-positions, respectively. This behavior is well shown if one compares the results for the unsubstituted compound (K - 1200 M" ,). 4-methyl-A-4-thiazoline-2-thione K = 2200 M ). and 5-methyl-4-r-butyl-A-4-thiazoline-2-thione K=120 M ) (58). 

The quatemization reaction of the thiazole nitrogen has been used to evaluate the steric effect of substituents in heterocyclic compounds since thiazole and its alkyl derivatives are good models for such study. In fact, substituents in the 2- and 4-positions of the ring only interact through their steric effects (inductive and resonance effects were constant in the studied series). The thiazole ring is planar, and the geometries of the ground and transition states are identical. Finally, the 2- and 4-positions have been shown to be different (259. 260). 

The importance of both electronic and steric effects is clear in cycloadditions as in cross-oxidations. One example is a heterocycHc modification leading to the thermodynamically less stable natural form of juglone derivatives such as ventiloquinones JT [124917-64-2] (84) and I [124917-65-3] (85) (83). The yields are 97% (84) from 6-chloro-2,3-dimethoxy-l,4-ben2oquinone [30839-34-0] and 100% (85) upon hydrolysis. 

Because of steric effects, TMXDI is less reactive than the trifunctional derivatives of hexamethylene diisocyanate (HDI) (1,6-diisocyanatohexane)... 

Pyrazole and its C-methyl derivatives acting as 2-monohaptopyrazoles in a neutral or slightly acidic medium give M(HPz) X, complexes where M is a transition metal, X is the counterion and m is the valence of the transition metal, usually 2. The number of pyrazole molecules, n, for a given metal depends on the nature of X and on the steric effects of the pyrazole substituents, especially those at position 3. Complexes of 3(5)-methylpyrazole with salts of a number of divalent metals involve the less hindered tautomer, the 5-methylpyrazole (209). With pyrazole and 4- or 5-monosubstituted pyrazoles M(HPz)6X2... 

Studies of the alkylation of indazoles (67HC(22)1) have been updated by Nunn (73JCS(PD2371) and Palmer (75JCS(P1)1695). The ratio of methylation at positions 1 and 2 is relatively sensitive to the steric effect of substituents at positions 3 and 7 as shown by the results obtained in basic medium for unsubstituted indazole (55 45) and its 3-phenyl (74 26) and7-nitro derivatives (29 71). 

Substitution reactions by the ionization mechanism proceed very slowly on a-halo derivatives of ketones, aldehydes, acids, esters, nitriles, and related compounds. As discussed on p. 284, such substituents destabilize a carbocation intermediate. Substitution by the direct displacement mechanism, however, proceed especially readily in these systems. Table S.IS indicates some representative relative rate accelerations. Steric effects be responsible for part of the observed acceleration, since an sfp- caibon, such as in a carbonyl group, will provide less steric resistance to tiie incoming nucleophile than an alkyl group. The major effect is believed to be electronic. The adjacent n-LUMO of the carbonyl group can interact with the electnai density that is built up at the pentacoordinate carbon. This can be described in resonance terminology as a contribution flom an enolate-like stmeture to tiie transition state. In MO terminology,.the low-lying LUMO has a... 

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

Correlations with o in carboxylic acid derivative reactions have been most successful for variations in the acyl portion, R in RCOX. Variation in the alkyl portion of esters, R in RCOOR, has not led to many good correlations, although use of relative rates of alkaline and acidic reactions, as in the defining relation, can generate linear correlations. The failure to achieve satisfactory correlations with cr for such substrates may be a consequence of the different steric effects of substituents in the acyl and alkyl locations. It has been shown that solvolysis rates of some acetates are related to the pA", of the leaving group, that is, of the parent alcohol. The pK of alcohols has been correlated with but this relationship... 

The DTBS group is probably the most useful of the bifunctional silyl ethers. Dimeihylsilyl and diisopropylsilyl derivatives of diols are very susceptible to hydrolysis even in water and therefore are of limited use, unless other structurally imposed steric effects provide additional stabilization. 

The Bsmoc derivative is formed from the chloroformate or the A -hydroxy-succinimide ester. It is cleaved rapidly by a Michael addition with tris(2-aminoethyl)amine at a rate that leaves Fmoc derivatives intact. More hindered bases, such as A -methylcyclohexylamine or diisopropylamine, do not react with the Bsmoc group, but do cleave the Fmoc group, illustrating the importance of steric effects in additions to Michael acceptors. 

Secondary steric effects of nitro groups are more easily detected by comparing the reactivities with those of aza derivatives. For example, in structure 20 the rate depression on passing from methyl to -butyl is only 2.5-fold and can be attributed to an inductive effect, whereas in structure 21 a similar change involves the factor 16, which can be attributed in part to steric inhibition of resonance (S.I.R.) of thep-N02 group (reaction with piperidine). 

Secondary steric effects of the same kind have been found in the reaction of methyl derivatives of 22 with aniline. A methyl group at position 6 has a 4-fold rate-diminishing effect (mainly inductive), but when positions 4 and 6 are both methylated the effect is 81-fold and is mainly of steric origin. 

The greater electron-releasing capacity of a w-C(CHs)8 group than a Tn-CHg group ( inductive order ) is seen from the above data. The reactivity of the <-butyl derivative is of value in studies concerned with the steric effect of the NOg-activated analogues of A-heterocyclic compounds (Section IV, A, 2). 

The cation of 4,4 -biquinazolinyl and its 2,2 -dimethyl derivative readily add water across the 3,4- and 3, 4 -double bonds, but the cation of 2,2 -biquinazolinyl is not hydrated. Hydration in the 4,4 -isomers has been attributed to restricted rotation about the 4,4 -bond, a steric effect which is relieved by hydration. The ultraviolet spectrum of 2,2 -biquinazolinyl (neutral species and cation) shows that there is considerable conjugation between the quinazoline groups. Covalent hydration is absent from the latter compound because it would otherwise destroy the extended conjugation present. 

The low yields of 6,6 -disubstituted-2,2 -bipyridincs recorded in Table I are probably the result of steric retardation of the adsorption of 2-substituted pyridines. This view is supported by the observation that 2-methylpyridine is a much weaker poison for catalytic hydrogenations than pyridine. On the other hand, the quinolines so far examined (Table II) are more reactive but with these compounds the steric effect of the fused benzene ring could be partly compensated by the additional stabilization of the adsorbed species, since the loss of resonance energy accompanying the localization of one 71-electron would be smaller in a quinoline than in a pyridine derivative. 

The reaction is quite susceptible to steric effects since hindered secondary hydroxyl groups were found to be unreactive. The method can therefore be used to selectively replace a primary hydroxyl group by halogen in the presence of more hindered secondary hydroxyl groups in the same molecule. An example (70) is the reaction of 52 with triphenylphosphite methiodide which affords the 6-deoxy-6-iodo derivative 53 (60%) in which the C-2 hydroxyl group remains intact. 

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