Cyclisation rate

This author is perfectly aware that he could add very little to the work done by these workers if an attempt was made to focus on intramolecular catalysis phenomena or on the relevance to cyclisation of available models of chain conformation and chain dynamics instead, the aim will be the presentation of a general treatment of the subject, namely, one that includes the cyclisation of very short chains as well as that of very long chains of, say, 100 atoms or more. With a subject as vast as this, an encyclopaedic review would be a hopeless task. Therefore, the subject will be treated in a systematic and critical way, with more concentration on reaction series with regular and wide variations in structure, rather than on scattered examples. The aim will be to show that the field of intramolecular reactions is a mature area in which the merging of concepts from both physical organic chemistry and polymer chemistry leads to a unified treatment of cyclisation rates and equilibria in terms of a few simple generalisations and theories. 

An alternative approach, which is usual among physical organic chemists, involves a comparison of changes of thermodynamic quantities for structurally-related reaction series. Such an approach, for which the term extrathermodynamic is widely used (Leffler and Grunwald, 1963), will be adapted here in an appropriate form to the interpretation of chain-length effects on cyclisation rates and equilibria. The experimental basis is provided by cyclisation reactions for which either 0AS+- or 0AS -data are available. 

Figure 27 shows plots of all the available EM s for closures of small- and common-sized saturated carbocycles and heterocycles by intramolecular nucleophilic displacement. Clearly, a-values as small as 0.1 would be required in order to calculate extrathermodynamically from (67) EM-values comparable to those actually observed for ring-sizes 3 and 4, and an even smaller value would be necessary for ring-size 5. This would lead to the conclusion that the effect of ring strain on cyclisation rates is insignificant. The same conclusion was recently drawn by Benedetti and Stirling (1983), based on rates and activation parameters for the cyclisation of bis-sulphonyl-stabilised carbanions to 3-, 4-, and 5-membered bis-sulphonylcyloalkanes. 

The kinetic data in Scheme 2 illustrate the fact that radical cyclisation rates decrease as the chain length of the unsaturated radical increases. Furthermore, the chains become more flexible, and consequently the regioselectivity between the exo and endo cyclisation modes also decreases. From a synthetic perspective, the consequences of these factors are first, that uncy-clised materials often appear as by-products and second, that it is difficult to... 

Chemical Properties. - 2-Phenylthiazolidine reacts with isocyanates RNCO (R=alkyl, aryl) to form products derived from reaction at N and the 4-position of the phenyl ring1 . Ultraviolet irradiation of some thiazolidine spirochromenes (163 R=H, Me,Et,R1=H,Me,R2=H, alkyl,alkoxy,R =alkyl, etc.) gives photomerocyanines (164) which thermally revert to (163) The cyclisation rates and substituent effects were determined. The stability of (164) was increased... 

Rajanna et al. also demonstrated dramatic rate enhancements when ultrasonically irradiated Meth-Cohn quinoline syntheses were performed again, deactivated aeetanilides 20 were found to undergo efficient cyclisation in good yield. 

Rates of cyclisation in mixture of ammonium sulphate and sulphuric acid were also measured377. Although acidity functions were not known for such media, the logarithms of the rate coefficients (Table 99) correlated with [H2S04]/[HS0X ]... 

This chapter is concerned with reaction rates, equilibria, and mechanisms of cyclisation reactions of chain molecules. A detailed analysis of the historical development of experimental approaches and theories concerning the intramolecular interactions of chain molecules and the processes of ring closure is outside the scope of this chapter. It must be borne in mind, however, that the present state of the art in the field is the result of investigations which have been approached with a variety of lines of thought, methods, and objectives. 

Finally, there is a large body of experimental and theoretical contributions from investigators who are mainly interested in the dynamic and conformational properties of chain molecules. The basic idea is that the cyclisation probability of a chain is related to the mean separation of the chain ends (Morawetz, 1975). Up to date comprehensive review articles are available on the subject (Semiyen, 1976 Winnik, 1977, 1981a Imanishi, 1979). Rates and equilibria of the chemical reactions occurring between functional groups attached to the ends or to the interior of a flexible chain molecule are believed to provide a convenient testing ground for theories of chain conformations and chain dynamics in solution. 

In their pioneering work on the lactonisation of an extensive series of co-hydroxycarboxylic acids, Stoll et al. (1934) proposed a procedure for determining the specific rate for cyclisation from the yield of the monomeric lactone at the end of the reaction. To this end they considered the simplified... 

Thus, within the approximations on which scheme (1) is based, the yield Y/( 1 + Y) of ring product is solely determined by the value of the initial monomer concentration relative to the kintra/kdim ratio, which Stoll et al. termed the cyclisation constant C. C has units of mol 1 1 and represents the monomer concentration at which intra- and intermolecular processes occur at the same rate. That Stoll et al. disregarded the fact that two monomer units are used up in the intermolecular condensation, as well as that the monomer disappears by reaction with functional groups at the ends of polymer chains was pointed out by Morawetz and Goodman (1970), who proposed an alternative approximate solution to the problem, as based on... 

For a system which is well-described by scheme (6) the rate equation is (8) where C is Stoll s cyclisation constant (Galli et al., 1973). Equation (8) is a... 

In the same year in which Stoll et al. (1934) defined the cyclisation constant C, Kuhn (1934) laid the foundations of the theoretical approaches to the conformational statistics of hydrocarbon chains and considered the cyclisation probability of the chain as a fundamental, chain length dependent phenomenon related to chain shape. He proposed to view the specific rate kintra of an intramolecular reaction between a pair of reactive groups attached to the ends of a chain molecule as the product of the effective concentration Ceff of... 

Relative rates and approximate cyclisation constants C for the cyclisation of... 

Approximate relative rates of cyclisation of o-bromoalkoxyphenoxides [1] to catechol... 

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