Intermolecular Cyclic Transition State Reactions

The quinolizinium ring can behave as the diene component in reverse electron demand Diels-Alder reactions. For example (Equation 1), the reaction between a dienophile generated in situ by acid-catalyzed dehydration of precursor 72 and quinolizinium 73 gave the l,4-ethanobenzo[A]quinolizinium derivative 74 2001BML519 . 

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Intra- and intermolecular reactions with cyclic transition states. Reactions of these types are discussed in Sections 3.2.1.2 and 3.2.1.10, respectively due to the reduced aromaticity and polarizability, reactions of these types are of considerable importance. 

The effective molarity (EM) is formally the concentration of the catalytic group (RCOO- in [5]) required to make the intermolecular reaction go at the observed rate of the intramolecular process. In practice many measured EM s represent physically unattainable concentrations, and the formal definition is probably relevant only in reactions (which will generally involve very large cyclic transition states) where the formation of the ring or cyclic transition state per se is enthalpically neutral, or in diffusion-controlled processes. For the formation of small and medium-sized rings and cyclic transition states the EM as defined above contains, and may indeed be dominated by, the enthalpy of formation of the cyclic form. This topic has been discussed briefly by Illuminati et al. (1977) and will be treated at greater length in a future volume in this series. 

Workers in three laboratories have studied ligation via cyclic transition-state intermediates. The couplings described in Section 5.1.10.1 to form the amide or thioester bond involve second-order intermolecular reactions of two peptide components, which are necessarily... 

The intramolecular methylation of the substrate of Figure 2.6, which was not observed, would have had to take place through a six-membered cyclic transition state. In other cases, cyclic, six-membered transition states of intramolecular reactions are so favored that intermolecular reactions usually do not occur. Why then is a cyclic transition state not able to compete in the SN reactions in Figure 2.6 ... 

Thermal intermolecular reactions with cyclic transition states have so far not been investigated in the pteridine series despite the facts that transformations of this type are characteristic of compounds with low aromaticity. 

A positive charge perturbs the electron distribution and thus reduces the aromaticity of a six-membered cationic ring. As expected, reaction with free radicals and reactions via cyclic transition states (both intra- and intermolecular) are facilitated. The uptake of an electron to form a neutral radical is especially easy. 

For R = hydrogen, methyl or ethyl, the e.s.r. spectrum of the corresponding vinyl radical was observed, showing that no reaction had occurred. This lack of reaction is not surprising as the radicals cannot adopt a suitable configuration for reaction. It also shows that the vinyl radicals are sufficiently isolated from unreacted vinyl halide molecules to prevent the occurrence of intermolecular hydrogen abstraction. However, when R = propyl, a six-membered cyclic transition state can be formed and in fact the spectrum of the vinyl radical is completely replaced by that of the alkyl radical formed by abstraction from the terminal methyl group (reaction 32). 

Section IIB). Either 35 or 36 probably applies in general for other substrates, though cyclic transition states cannot be ruled out. The general acid transition state 37 can be considered unlikely in view of the fact that few intermolecular general acid-catalyzed ester hydrolysis reactions are known. Water undoubtedly does, however, play an important role in solvation of the carbonyl oxygen in the transition state. 

One of the determining factors in reaction rates is how frequently the reaction partners collide. If collisions are more frequent, the reaction rate will be faster. Increasing the concentration of a reactant invariably increases the collision frequency and therefore the reaction rate. If the nucleophile and electrophile are part of the same molecule, they may collide much more often than is possible in even the most concentrated solutions. Therefore intramolecular reaction rates can easily exceed intermolecular rates. The energy of the cyclic transition state for an intramolecular process depends on the rigidity and size of the loop of atoms in the cyclic transition state and on the orbital alignment restrictions of the process involved. 

Intermolecular reactions with cyclic transition states... 

We claim, however, that this reaction is likely to be more complex. The isolated intermediate salt may be the prototropic isomer 4.23 formed intermolecularly from 4.21, which is the primary steady-state intermediate. Compound 4.23 is energetically more favorable because in 4.23 — in contrast to 4.21 — conjugation (Ti-orbital overlap) between the arylcarbonyl part and the 4-toluenesulfonyl azide part is not interrupted by an sp C-atom. Intermediate 4.21 may, however, also react directly to give the diazoketone 4.22 via a cyclic transition state 4.24 that contains, however, a less favorable (Z)-azo group. The prototropy 4.21 4.23 was included at an early date for the mechanism of the diazo transfer from 4-toluenesulfonyl azide to the cyclopentadienyl anion by Roberts (see review Roberts, 1990, p. 217) and by Huisgen (1990). A transition state similar to 4.24 was mentioned by Balli et al. (1974) for the diazo transfer of azidinium salts to pyrazolin-5-one and 5-aminopyrazole compounds (see below). 

Like Norrish type I reaction, the intermolecular 1, 5-hydrogen transfer to alkoxy radical involves a six memhered cyclic transition state structure, as demonstrated by the photolysis of series of co-phenylalkyl nitrites. 

As mentioned above, it is known that intramolecular chain transfer, in particular, 1,5-hydrogen shift, does also occur during the polymerization of monomers that yield very reactive macroradicals, such as acrylates and acrylic acid. This so-called backbiting reaction, by which a secondary radical (SPR) is transformed into a more stabilized tertiary (MCR) one, proceeds via a six-membered cyclic transition state with rate coefficient kbb (see Scheme 1.17). In principle, intramolecular chain transfer to a remote chain position and intermolecular chain transfer to another polymer molecule may also take place.These latter processes are, however, found to be not significant in butyl acrylate polymerization at low and moderate degrees of monomer conversion and temperature. ... 

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