Activation energy, cyclization

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

The activation energy of the reaction of thermal cyclization of PAN containing 5% of thioamide groups amounts to 20 kcal/mol (83,7 kJ/mol). 

In a seminal work, Koga and Morokuma suggested that the high activation energy of the Bergman cyclization is due to the strong electron repulsion between the... 

In particular, the N02, CF3, syn-CHO, and syn-OMe groups were predicted to decrease the activation energy for Bergman cyclization by destabilizing reactants through steric repulsion between the orr/zu-substituent and the in-plane acetylenic... 

Fig. 12 Correlation between the calculated activation energy of the Bergman cyclization and the product of natural charges at the terminal acetylenic atoms of benzannelated enediynes. Only para substituents obey the correlation. Adapted from reference49.

Sterically compact ortho substituents such as Me, OH, anti-OMe, F, Cl, and CN destabilize the ground and transition states to a similar degree. As a result, changes in the activation energy are minor. The net effect of these substituents on the cyclization rate is similar to that of the para substituents, and the corresponding computational data fit well into the correlation in Fig. 12.49... 

These computational predictions have been tested experimentally. Kinetic measurements confirmed that both ortho-N02 and ortho-CHO substituents substantially decrease activation energies for the Bergman cyclization supporting earlier computational predictions.51... 

Since four-electron repulsion is the dominant factor in the reactant destabilization, any structural perturbation that either increases electron repulsion in the reactant or decreases the electron repulsion in the TS will decrease the activation energy for the cyclization. One way for placing an accelerating substituent in direct spatial proximity to the in-plane re-orbitals is to use appropriate ortho substituents in benzannelated enediynes. 

Fig. 17 The Bergman cyclizations of parent and fluoro-substituted enediynes with the triple bond and the incipient bond lengths and the activation energies calculated at the BS-UB3LYP/6-31G level.

Bergman cyclization, 3, 16, 25 acid-catalyzed, 20 activation energy, 10-11 deceleration of, 12, 12/... 

In Case 1 both the ring closure steps (with rate constants ks and kR) are faster than dissociation of the 7r-complexes to reform the alkenol and N-X+ species. Here the [S]/R] product ratio is determined only by the difference in the activation energy leading to the 7is- and rcR-complexes because immediately after these are formed the cyclization occurs. Thus, the chirality is set by the approach of the alkene to the halonium ion. 

The transition structure trans-42 to fra s-43 TiCp2Cl was also calculated and a barrier of 11.7 kcal mol 1 was obtained for the cyclization. This value is similar to the activation energy for the formation of cis-43 TiCp2Cl, although the distance between the carbon-centered radical and oxygen atom is shorter (2.04 A). 

Ab initio calculations on the equilibrium between (14a) and (14b) are carried out with the 3-21G basis set. Figure 4 shows a plot of the calculated activation energy E vs. the reaction energy AE for the cyclization reactions. The plot is linear and provides a striking confirmation of Hammond s postulate. The cyclic structures (14b) are found to be planar, while the terminal =NH group in (14a) is ca. 50° out of the plane formed by the other atoms in (14a) <90CC882>. The gas phase basicity and acidity of 1,2,3-triazole have been calculated by ab initio methods (6-31G //6-31G) and compared with experimental values <89MI 401-01 >... 

Figure 4 Plot of activation energy vs. reaction energy for the cyclization reactions.

Ab initio and density functional calculations have been carried out on the mechanism of the 1,5-electrocyclization reactions of conjugated nitrile ylides (190). The results indicate that vinyl-conjugated systems (306) (X = CH2) cyclize via the classical electrocyclization pathway—a pericyclic, monorotatary process with a relatively early transition state in which there is substantial torsion of the vinyl group as well as pyramidalization at C(5). In contrast, systems with a heteroatom at the cyclization site 306 (X=NH, O) react via a pseudo-pericyclic process that is characterized by the in-plane attack of the lone pair of the heteroatom on the nitrile ylide. Such reactions have a lower activation energy. 

In the case of insertion toward fluorine (41), there is an even greater amount of positive-positive charge repulsion between the ortho and ipso carbons than in the transition state and this effect is responsible, in part, for a higher activation barrier for insertion toward F to form 41 than away from fluorine to form 40. Therefore, the origin of the pronounced influence of ortho,ortho-difluoro substitution on the lifetime of singlet arylnitrene and the increased activation energy of its cyclization is the result of combination of the steric effect and the extraordinary electronegativity of fluorine atom. 

The kinetics of the reaction between o-phenylenediamine and phenacyl bromide has been investigated and found to be a two-step process (Eq. 1). The intermediate 10 cyclized to give the dihydrophenylquinoxaline (11). The first stage is characterized by second-order kinetics and has an activation energy of 9.70 kcal/mole the second stage has an activation energy of 12.5 kcal/mole.13... 

Ab initio calculations on the equilibrium between (102) and (103) are carried out with the 3-21G basis set. The plot of the calculated activation energy Ea vs. the reaction energy AEr for the cyclization reactions is linear and that provides a striking confirmation of Hammond s postulate. 

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