Intermolecular Reactions with Cyclic Transition States

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. 

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. 

Intermolecular reactions with cyclic transition states... 

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. 

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. ... 

Stereochemical and kinetic analyses of the Brpnsted acid-catalysed intramolecular hydroamination/deuterioamination of the electronically non-activated cyclic alkene (13) with a neighbouring sulfonamide nucleophile have been found to proceed as an anh-addition (>90%) across the C=C bond to produce (15). No loss of the label was observed by and NMR (nuclear magnetic resonance) spectroscopies and mass spectrometry (MS). The reaction follows the second-order kinetic law rate = 2 [TfOH] [13] with the activation parameters being = 9.1 0.5 kcal moP and = -35 5 cal moP An inverse a-secondary kinetic isotope effect of d/ h = (1-15 0.03), observed for (13) deuteration at C(2), indicates a partial CN bond formation in the transition state (14). The results are consistent with a mechanism involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C(3) position coupled with an intramolecular anti-addition by the sulfonamide group. ... 

Molecularity vs. Mechanism. Cyclization Reactions and Effective Molarity A useful illustration of the distinctions between mechanism, molecularity, and order arises in the analysis of intramolecular versions of typically intermolecular reactions. Consider a classic Sn2 reaction of an amine and an alkyl iodide. The reaction is second order (first order in both amine and alkyl iodide) and bimolecular (two molecules involved in the transition state that s what the "2" in "Sn2" Stands for). The mechanism involves the backside attack of the nucleophilic amine on the C, displacing the iodide in a single step. Now consider a long chain molecule i that terminates in an amine on one end and an alkyl iodide on the other. Now two types of Sn2 reactions are possible. If two different molecules react, we still have a second order, bimolecular, intermolecular reaction. The product would ultimately be a polymer, ii, and we will investigate this type of system further in Chapter 13. Alternatively, an intramolecular reaction could occur, in which the amine reacts with the iodide on the same molecule producing a cyclic product. Hi. This is still called an S 2 reaction, even though it will be first order and unimolecular. 

These phenomena can be explained as follows. First, in the absence of water or in the presence of a small amount of water, THF predominantly coordinates to Yb(OTf)3 and the activity of THF-coordinated Yb(OTf)3 as a Lewis acid is low. The reaction proceeds slowly via the cyclic six-membered transition state with anti preference [24]. On the other hand, when the moles of water are gradually increased, water is prone to coordinate to Yb(OTf)3 instead of tetrahydrofuran (THF), and Yb(OTf)3 dissociates to form the active Yb cation. The solid-state structure of Yb(0Tf)3 9H20 has been investigated [7dj. When Yb(0Tf)3 9H20 (prepared according to the literature) was used, the aldol reactions proceeded, but faster hydrolysis of the silyl enol ethers was observed. At this stage, intramolecular and intermolecular exchange reactions of water molecules occur frequently [25]. There is a chance for an aldehyde to coordinate to Yb instead of to water molecules and the aldehyde is activated ... 

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