Cyclization parameter

Despite the contribution of the above factors, it is clear that bending of the two alkyne moieties toward each other increases the energy of the system as illustrated by the three plots in Fig. 7.24 These plots illustrate the relation between the ring size and calculated cyclization parameters in more detail and dependence of the total energy of the system from the c-d distance. Interestingly, simple bending of alkyne moiety reproduced the effect of cyclic restraints reasonably well. A similar conclusion has been reached even earlier by Kraka and Cremer.40... 

As the examples mentioned above show, a variety of experimental procedures for cyclizations under dilution conditions exist. Up to this day no generaly applicable procedure is known also, the determination of cyclization parameters to a given target molecule is based on the experiences made by synthesizing similar compounds. Each new structure requires precise conditions for its synthesis often a small window has to be hit with regard to the reaction conditions. 

Katritzky and co-workers investigated the cyclization parameters for ortho-diazo compounds in the benzene series (64JCS751) and determined that if substituents X and Y are aryls, the compounds exist as the ring-open form 138. If one of the substituents is electron withdrawing, for instance, CN or PhSO2, the 1-aminobenzotriazole structure 139 is favored. 

Let us specifically consider telechelic polymers. The intramolecular association of telechelic polymers is unique, namely, they form a single loop (petal). The probability to form such a loop is decided by the thermodynamic equilibrium condition. It is given by the cyclization parameter introduced in Section 6.2 [30]... 

DuSek and Ilavsky have presented a mean-field model which can describe the amount of cyclization reasonably well when a cyclization parameter is properly adjusted However, this model requires a very high chain flexibility and it does not treat shielding of pendent groups and trapping of radicals. 

An important reaction parameter is the choice of the base and NajCO or NaOAc have been shown to be preferable to EtjN in some systems[2]. The inclusion of NH4CI has also been found to speed reaction[2]. An optimization of the cyclization of A -allyl-2-benzyloxy-6-bromo-4-nitroaniline which achieved a 96% yield found EtjN to be the preferred base[3]. The use of acetyl or inethanesulfonyl as N-protecting groups is sometimes advantageous (see Entries 4 and 5, Table 4.1). 

The Fischer cyclization has proved to be a very versatile reaction which can tolerate a variety of substituents at the 2- and 3-positions and on the aromatic ring. An extensive review and compilation of examples was published several years ago[3]. From a practical point of view, the crucial reaction parameter is often the choice of the appropriate reaction medium. For hydrazones of unsymmetrical ketones, which can lead to two regioisomeric products, the choice of reaction conditions may determine the product composition. 

This conclusion is valid also for the isomerizations involving cyclization of diazides 344a (R = Na.Y = CH) [74JOC1778 76AHC(Sl),p. 498]. Thermodynamic and kinetic parameters of type 344a 344b interconversion... 

Activation parameters. Calculate AW and AS for the cyclization of the 5-hexenyl radical, whose rate is given in Eq. (5-39). 

Incineration of a collection of polymers with 10 different kinds of brominated flame retardants has been studied under standardized laboratory conditions using varying parameters including temperature and air flow. Polybrominated diphenyl ethers like the deca-, octa-, and pentabromo compounds yield a mixture of brominated dibenzofurans while burning in polymeric matrices. Besides cyclization, debromination/hydrogenation is observed. Influence of matrix effects and burning conditions on product pattern has been studied the relevant mechanisms have been proposed and the toxicological relevance is discussed. 

What determines the propensity of cyclization of the different diethynylated complexes Looking carefully at the monomers, there are three variables which could influence the formation of cycles as opposed to linear polymers. One is the angle a between the two alkyne arms. The second is the parameter /, which indicates how far the two alkyne groups are apart at their origin, while the third is the parameter the bulk of the monomer. 

Figure 7.26. Photo-induced hydrogen abstraction from the y-carbon leads to biradical 72, which can (a) revert to the starting ketone, (b) cyclize, or (c) cleave the 2,3-CC bond. The structure for y-H abstraction for the starting ketone is also shown and the ideal parameters defined and listed.

From the parameters highlighted, it can be seen that the p value for 78s is smaller or closer to 0°, than that in 79s and thus preference for cyclization prevails over cleavage. On the contrary, for 79s the values that would favor cleavage are also closer to 0° than in 78s. Not only do these values indicate that 79s is prone to cleavage, but comparing the % and 4 values to those in parenthesis, it is C2-C3 bond that cleaves preferentially over the C2-C3.. These parameters suggest that very small conformational changes may have drastic effects in the chemo-selectivity of biradicals. 

The stability of a trivial assembly is simply determined by the thermodynamic properties of the discrete intermolecular binding interactions involved. Cooperative assembly processes involve an intramolecular cyclization, and this leads to an enhanced thermodynamic stability compared with the trivial analogs. The increase in stability is quantified by the parameter EM, the effective molarity of the intramolecular process, as first introduced in the study of intramolecular covalent cyclization reactions (6,7). EM is defined as the ratio of the binding constant of the intramolecular interaction to the binding constant of the corresponding intermolecular interaction (Scheme 2). The former can be determined by measuring the stability of the self-assembled structure, and the latter value is determined using simple monofunctional reference compounds. 

Pioneering studies of Trost and his co-workers have explored all the parameters of this reaction. An interesting piece of work has, for instance, shown that the presence of an ether or a silyl ether in a substrate also exerts a profound effect on the regioselectivity of the cyclization. Thus, a silyl ether group at the allylic position (202) furnishes the corresponding 1,3-diene 203, whereas an ether group at the homoallylic position gives exclusively the 1,4-diene 205 (Scheme 50).210... 

Aldol reaction of keto-acid 21 with aldehyde 10 and esterification of the resulting acids with alcohol 22 led rapidly to cyclization precursor 23 and its 6S,7R-diastereomer (not shown). RCM using ruthenium initiator 3 (0.1 equiv) in dichloromethane (0.0015 M) at 25 °C afforded macrolactones 24a and 24b in a 1.2 1 ratio. Deprotection and epoxidation of the desired macrolactone, 24a, afforded epothilone A (4) via 25a (epothilone C) (Scheme 5). Varying a number of reaction parameters, such as solvent, temperature and concentration, failed to improve significantly the Z-selectivity of the RCM. However, in the context of the epothilone project, the formation of the E-isomer 24b could actually be viewed as beneficial since it allowed preparation of the epothilone A analog 26 for biological evaluation. 

Rate parameters for some decycUzation processes are also presented in Table XI. From the principles of detailed balancing, rate parameters for the reverse reactions, i.e., cyclizations, can be calculated. 

One of the most important parameters to determine the reactivity is the distance between the thiocarbonyl sulfur (S) and the alkenyl carbon atom (C6) in Table 1, because a new bond will be formed between these two atoms at the initial step of the photoprocess. The actual distance of the (Z,E)-conformation imide la is 3.59 A, which is closely placed and is almost the same as the sum of the van der Waals radii 3.50 A. In the (EyE) conformation, the atomic distances are longer than that of la, and are 4.13 A for Ic and 4.32 A for Id. For the second step of cyclization, the atomic distance between the thiocarbonyl carbon (C2) and the alkenyl carbon (C5) is in the range from 3.00 to 3.11 A, which is much smaller than the sum of the van der Waals radii 3.40 A. From this geometrical consideration of the site of the new bond formation, it is expected that the reaction leading to thietane will smoothly progress. 

On the basis of these parameters we determined two possible transition states, 22 and 23. In transition state 22, the rhodium carbene is pointed away from the flip of the incipient cyclopentane ring (a chair-like transition state, counting the five carbons and the rhodium in the six-membered ring), whereas in 23 the rhodium carbene is pointed toward the flip of the incipient cyclopentane ring (a boat-hke transition state). As 10 (see Scheme 16.3) cyclizes to 12, in which the methyl and the phenyl are on the same face of the cyclopentane, we concluded that at the point of commitment to product formation, the transition state leading to cyclization must be chair-like 22 rather than boat-like 23. 

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