Transition state substitution

Because carbocatwn character develops at the transition state substitution is favored at the carbon that can better support a developing positive charge Thus m... 

The propenyl group can then supply electrons to the cobalt atom by a resonance effect. This basic mechanism may also be applied to explain the marked accelerating effect of the aroyl group. Except in cases where ortho substitution sterically hinders formation of a cyclic transition state substitution on the aromatic ring has relatively little effect on the rate of decomposition. 

Honeyman147 reported the synthesis of methyl 2,3-anhydro-/3-L-lyxopyranoside, and claimed that, on alkaline hydrolysis, this gives a 2 1 ratio of L-xyloside L-arabinoside, but these results could not be substantiated by Buchanan and R. Fletcher,68 who recorded different constants for the epoxide and for the disulfonic ester claimed147 to be the starting material for its synthesis. The same epoxide has been synthesized by Reist and coworkers,160 and its properties are in agreement with Buchanan and Fletcher s results. Ethyl or methyl 3,4-anhydro-/3-L-ribopyranoside undergoes substitution at C-4 in all the reactions thus far studied. Neither half-chair conformation would seem to be clearly favored, but the specificity observed can be rationalized by considering the steric and polar interactions that may arise in the transition state substitution at C-3 in conformation 58 would involve marked interactions between the nucleophile and... 

Inspection of Fig. 8 suggests that the discrepancy in the additivity relationship for multiple substitutions is most serious when the first substituent is strongly ED or EW (s-ED, s-EW). A transition state substituted by a s-EW group is more electron deficient than it is in the unsubstituted (Y = H) series, so that the electron demand in such a transition state must be more than that in the parent system. Consequently, the p-value for the Y = P-NO2 series is larger than that for the Y = H series. On the other hand, when the Y-substituent is s-ED, such as p-methoxy, then a smaller p results for the series. From these arguments, it is apparent that a change in the extent of electron deficiency in the transition state must be a function of the ED or EW power of the first substituent. TTiis effect can be expressed quantitatively by (6) and (7). 

Because carbocation character develops at the transition state, substitution is favored at the carbon that can better support a developing positive charge. Thus, in contrast to the reaction of epoxides with relatively basic nucleophiles, in which SN2-like attack is faster at the less crowded carbon of the three-membered ring, acid catalysis promotes substitution at the position that bears the greater number of alkyl groups ... 

Figure 2.3 Potential energy surface of the reaction, as well as schematic presentation of [(PDIjCalTHFjj] catalyzed donor-donor (D/D)- the reactants, intermediates, transition states, substituted NjCPhj diazocarbene decom- and product of this reaction. Energies are position and metallocarbene formation presented as A/fgjjCAGgjjIfAGjoi]...

SCHEME 2.98 Zimmennan-Traxler transition state (substitution at boron atom has been removed for clarity). 

Preference for endo or exo transition state depends on the substitution of the diene, dieneophile and connecting chain. 

For electrophilic substitutions in general, and leaving aside theories which have only historical interest, two general processes have to be considered. In the first, the 5 3 process, a transition state is involved which is formed from the aromatic compound, the electrophile (E+), and the base (B) needed to remove the proton ... 

At one time a form of 8 2 mechanism was favoured for electrophilic substitution in which in the transition state bonding between carbon and the electrophile and severance of the proton had proceeded to the... 

The picture of the process of substitution by the nitronium ion emerging from the facts discussed above is that of a two-stage process, the first step in which is rate-determining and which leads to a relatively stable intermediate. In the second step, which is relatively fast, the proton is lost. The transition state leading to the relatively stable intermediate is so constructed that in it the carbon-hydrogen bond which is finally broken is but little changed from its original condition. 

However, the electronic theory also lays stress upon substitution being a developing process, and by adding to its description of the polarization of aromatic molecules means for describing their polarisa-bility by an approaching reagent, it moves towards a transition state theory of reactivity. These means are the electromeric and inductomeric effects. 

Wheland intermediate (see below) as its model for the transition state. In this form it is illustrated by the case mentioned above, that of nitration of the phenyltrimethylammonium ion. For this case the transition state for -nitration is represented by (v) and that for p-substitution by (vi). It is argued that electrostatic repulsions in the former are smaller than in the latter, so that m-nitration is favoured, though it is associated rvith deactivation. Similar descriptions can be given for the gross effects of other substituents upon orientation. 

M.o. theory and the transition state treatment In 1942 Wheland proposed a simple model for the transition state of electrophilic substitution in which a pair of electrons is localised at the site of substitution, and the carbon atom at that site has changed from the sp to the sp state of hybridisation. Such a structure, originally proposed as a model for the transition state is now known to describe the (T-complexes which are intermediates in electrophilic substitutions... 

The model adopted by Ri and Eyring is not now acceptable, but some of the more recent treatments of electrostatic effects are quite close to their method in principle. In dealing with polar substituents some authors have concentrated on the interaction of the substituent with the electrophile whilst others have considered the interaction of the substituent with the charge on the ring in the transition state. An example of the latter method was mentioned above ( 7.2.1), and both will be encountered later ( 9.1.2). They are really attempts to explain the nature of the inductive effect, and an important question which they raise is that of the relative importance of localisation and electrostatic phenomena in determining orientation and state of activation in electrophilic substitutions. 

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

Streitwieser pointed out that the eorrelation whieh exists between relative rates of reaetion in deuterodeprotonation, nitration, and ehlorination, and equilibrium eonstants for protonation in hydrofluorie aeid amongst polynuelear hydroearbons (ef. 6.2.3) constitutes a relationship of the Hammett type. The standard reaetion is here the protonation equilibrium (for whieh p is unity by definition). For eon-venience he seleeted the i-position of naphthalene, rather than a position in benzene as the referenee position (for whieh o is zero by definition), and by this means was able to evaluate /) -values for the substitutions mentioned, and cr -values for positions in a number of hydroearbons. The p -values (for protonation equilibria, i for deuterodeprotonation, 0-47 for nitration, 0-26 and for ehlorination, 0-64) are taken to indieate how elosely the transition states of these reaetions resemble a cr-eomplex. 

The more extensive problem of correlating substituent effects in electrophilic substitution by a two-parameter equation has been examined by Brown and his co-workers. In order to define a new set of substituent constants. Brown chose as a model reaction the solvolysis of substituted dimethylphenylcarbinyl chlorides in 90% aq. acetone. In the case ofp-substituted compounds, the transition state, represented by the following resonance structures, is stabilized by direct resonance interaction between the substituent and the site of reaction. 

The suitability of the model reaction chosen by Brown has been criticised. There are many side-chain reactions in which, during reaction, electron deficiencies arise at the site of reaction. The values of the substituent constants obtainable from these reactions would not agree with the values chosen for cr+. At worst, if the solvolysis of substituted benzyl chlorides in 50% aq. acetone had been chosen as the model reaction, crJ-Me would have been —0-82 instead of the adopted value of —0-28. It is difficult to see how the choice of reaction was defended, save by pointing out that the variation in the values of the substituent constants, derivable from different reactions, were not systematically related to the values of the reaction constants such a relationship would have been expected if the importance of the stabilization of the transition-state by direct resonance increased with increasing values of the reaction constant. 

The influence of alkyl groups has been attributed to the +/ effect operating primarily at the 0- and />-positions (i), and somewhat less strongly at the m-position by relay. Alternatively, the effect is seen as stabilising the transition states for 0- and />-substitution (ii), more than... 

A different explanation of the high 0 -ratios is based on the view, for which there is some evidence, that in a transition state for substitution which resembles the Wheland intermediate in structure there is a larger positive charge at the - than at the o-position. Substituents of the present type would therefore stabilise the transition state more from the 0-than from the -position. ... 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

Alkylation by diazoalkanes gives more N-substituted product when the reaction goes through an S l transition state. Representative data are given in Table Vll-lOa. and they are discussed in Ref. 101. 

Another quantitative approach to the reactivity of thiazole (381) in reactions involving a cationic transition state, though not exactly of the electrophilic substitution type, deserves to be mentioned here because of... 

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