Intramolecular transition state

In this part, we will summarize some of our results on the investigation of the toluene intramolecular isomerization pathways." " Both cluster approach and periodic approach methods have been employed which allow giving an illustration of the consequence of the simplistic model in the cluster approach. H-Mordenite (H-MOR) zeolite is used for the periodic calculations. The toluene molecule does not have a problem to fit within the large 12-membered ring channels of this zeolite. Furthermore, the intramolecular transition states do not suffer from steric constraints. It is known that intramolecular aromatics isomerization can proceed via two different reaction pathways (see Figure 7). The first route proceeds through a methyl shift isomerization, whereas the second route involves a dealkylation or disproportionation reaction which results in the formation of a methoxy species and benzene as intermediate. 

Irradiation of pyran-4-ones with furans tethered to the 3-position 31 produced [4-1-3]-cycloadducts 32 and 33 (Table 81.3). The loss of the usual e do-selectivity in the cycloaddition was attributed to steric constraints in the compact intramolecular transition states. The reaction proved to be inefficient in nonpolar solvents such as CHjClj and required the use of TFE for optimum results. 

A situation that arises from the intramolecular dynamics of A and completely distinct from apparent non-RRKM behaviour is intrinsic non-RRKM behaviour [9], By this, it is meant that A has a non-random P(t) even if the internal vibrational states of A are prepared randomly. This situation arises when transitions between individual molecular vibrational/rotational states are slower than transitions leading to products. As a result, the vibrational states do not have equal dissociation probabilities. In tenns of classical phase space dynamics, slow transitions between the states occur when the reactant phase space is metrically decomposable [13,14] on the timescale of the imimolecular reaction and there is at least one bottleneck [9] in the molecular phase space other than the one defining the transition state. An intrinsic non-RRKM molecule decays non-exponentially with a time-dependent unimolecular rate constant or exponentially with a rate constant different from that of RRKM theory. 

Syntheses of alkenes with three or four bulky substituents cannot be achieved with an ylide or by a direct coupling reaction. Sterical hindrance of substituents presumably does not allow the direct contact of polar or radical carbon synthons in the transition state. A generally applicable principle formulated by A. Eschenmoser indicates a possible solution to this problem //an intermolecular reaction is complex or slow, it is advisable to change the educt in such a way. that the critical bond formation can occur intramolecularly (A. Eschenmoser, 1970). 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

The transition state for the rapid hydrolysis of the monoanion has been depicted as involving an intramolecular general acid catalysis by the carboxylic acid group, with participation by the anionic carboxylate group, which becomes bound at the developing electrophilic center... 

Each of the following molecules has been considered to be capable of some form of intramolecular catalysis of ester hydrolysis. For each reactant, indicate one or more mechanisms by which intramolecular catalysis might occur. Depict a transition-state arrangement that shows this catalysis. 

Substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. ° The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts position selectivity to the process ... 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

It has been proposed that oxygen adds to the excited keto group [- (112)]. The rearrangement of the resulting hydroxyhydroperoxy diradical (112) could then proceed by intramolecular hydrogen abstraction involving a six-membered cyclic transition state, followed by fission of the former C —CO bond to form the unsaturated peracid (113) as the precursor of the final product. Such a reaction sequence demands a hydrogen atom in the J -position sterically accessible to the intermediate hydroperoxy radical. 

Three kinetically equivalent rate terms involving intramolecular participation are shown in Table 6-3 with representations of appropriate transition states (mechanisms). Differentiation among these possibilities can be difficult. 

The formation of the less favored trisubstituted isomer (37) occurs by the usual intramolecular axial proton transfer from the 6 position, whereas that of the tetrasubstituted isomer (38) involves the intramolecular proton transfer of the stereoelectronically less favored equatorial proton either via a four-membered transition state (39) or a six-membered transition state (40). 

Factor b above is discussed in Sections II, B, 1 II, B, 4 and II, C. A hydrogen-bonded structure such as 221 can account for the facile reaction of 5-bromouracil or for the unique, so-called hydrolyzability of carboxymethylthio-azines (237). The latter may also react via the intramolecular mechanism indicated in 136. The hydrogen-bonded transition state 238 seems a reasonable explanation of the fact that 3,4,6- and 3,4,5-trichloropyridazines react with glacial acetic acid selectively to give 3-pyridazinones while other nucleophiles (alkoxides, hydrazine, ammonia, or sulfanilamide anion) react at the 4- and 5-positions. In this connection, 4-amino-3,5-dichloro-pyridazine in liquid hydrazine gives (95°, 3hr, 60%yield)the isomer-... 

Another such effect is the intervention of cyclic transition states in reactions of organometallic compounds (Section II, B, 5) with azines or in intramolecular nucleophilic substitutions (Section II, F). 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

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