Kinetics of cyclization

This apparent duality has led to certain misunderstanding and confusion and for the reader less acquainted with this field the relation between theoretical distribution predicted by Jacobson-Stockmayer theory and the distributions observed in real systems (frequently different from those predicted by the theory) could be not clear. Thus, in this section we describe the theories and then explain major experimental results in terms of the thermodynamics and kinetics of cyclization. 

The dependence of the pyrolysis on the sample structure may be used in applying Py-GC to solve various physico-chemical problems. In particular, Py-GC has been used to study the kinetics of cyclization of polyisoprene rubber the results were later corroborated by other methods [268,269]. 

This was supported by a study of the kinetics of cyclization of 38 and analogues with extra methylene groups inserted between the oxygen and alkyne groups to form analogues of 39. Overall, the reaction may be written as in the accompanying scheme. Insertion of alkynes into aminocarbene complexes of chromium is of potential use in synthesizing heterocycles. ... 

Van Speybroeck, V. Reyniers, M-F. Marin, G.B. Waroquier, M. The Kinetics of Cyclization Reactions on Polyaromatics from First Principles, CHEMPHYSCHEM 2002, 3, 863-870... 

In studies of the polymerization kinetics of triaUyl citrate [6299-73-6] the cyclization constant was found to be intermediate between that of diaUyl succinate and DAP (86). Copolymerization reactivity ratios with vinyl monomers have been reported (87). At 60°C with benzoyl peroxide as initiator, triaUyl citrate retards polymerization of styrene, acrylonitrile, vinyl choloride, and vinyl acetate. Properties of polyfunctional aUyl esters are given in Table 7 some of these esters have sharp odors and cause skin irritation. 

The ratio of products 15 and 16 is dependent on the structures, base, and the solvent. The kinetics of the reaction is likewise dependant on the structures and conditions of the reaction. Thus addition or cyclization can be the rate-determining step. In a particularly noteworthy study by Zimmerman and Ahramjian, it was reported that when both diastereomers of 20 were treated individually with potassium r-butoxide only as-epoxy propionate 21 was isolated. It is postulated that the cyclization is the rate-limiting step. Thus, for these substrates, the retro-aldolization/aldolization step reversible. ... 

Small amounts of cyclized products are obtained after the preparation of Grignard reagents from 5-hexenyl bromide.9 This indicates that cyclization of the intermediate radical competes to a small extent with combination of the radical with the metal. Quantitative kinetic models that compare competing processes are consistent with diffusion of the radicals from the surface.10 Alkyl radicals can be trapped with high efficiency by the nitroxide radical TMPO.11 Nevertheless, there remains disagreement about the extent to which the radicals diffuse away from the metal surface.12... 

Benzenediamine (129) gave 2-phenyl-3,4-dihydroquinoxaline (130) (AcONa, MeOH, reflux, CH4, 2 h 55% 783 with unsymmetric analogs of substrate (129), two isomers resulted in each case 783 and the kinetics of such cyclizations have been studied.821... 

Ring closure between an adjacent pair of aromatic substituents is also possible an example is the formation of indan from l-methyl-2-ethyl-benzene 11,109). In fact, Csicsery 109) found that the rate of cyclization of l-methyl-2-ethylbenzene to indan over platinum was somewhat faster than that of n-butylbenzene to methylindan, indicating that kinetically there is nothing to be gained by having ring closure at an aromatic carbon... 

Whereas Gold and Sghibartz showed that cation complexation depressed the rate of crown-ether disrupture, there is convincing evidence that crown ether formation is facilitated by the presence of cations. The template effect, presumably due to complexation of the open-chain precursor and formation of a crown-type conformation, clearly emerged from studies in which the yield of crown ethers was related to the type of cations present (Reinhoudt et al., 1976). Kinetic evidence for the template effect was presented by Mandolini and Masci (1977), who showed that the rate of cyclization of the precursor of benzo-18-crown-6 [2061 decreased in the order Ba2+ > SrJ+ > K+ > Na+ > Li+. This sequence is the same as the one found for the stability constants of the 1 1 complexes of these cations with 18-crown-6 in water (Table 3). 

Kricheldorf, H. R., Rabenstein, M., Maskos, M. and Schmidt, M., Macrocycles 15. The role of cyclization in kinetically controlled polycondensations. 1. Polyester synthesis, Macromolecules, 34, 713 (2001). 

Sequence inversion and racemization have been associated with uncatalyzed formation of the cyclic dipeptides and has been shown to greatly complicate the kinetics of formation. Cyclic dipeptide formation, by uncatalyzed processes, is rapid enough to pose an apparent threat to the stability of proteins and a possible rationale for the posttranslational N-acetylation of proteins that have been observed in higher organisms. The rate of DKP formation will also depend on the carbonyl ester protecting groups or the structures of the peptide-resin linkage in the solid-phase mode. Furthermore, cyclization is a concentration-independent reaction and demands the use of dilute solutions. ... 

The kinetics of the cyclization of 4-substituted benzamidoxime 4-nitrophenyl carbonates (34 X = H, Me, OMe, Cl, NO2) in the pH range 8-11 to yield the corresponding heterocycles (35) have been studied. At acidic pH, cyclization does not occur and the hydrolysis reaction predominates. 

Nitrobenzoylamino)-2,2-dimethylpropanamide (143 R = Me) reacts in methanol-DMSO solution with sodium methoxide to yield 5,5-dimethyl-2-(4-nitrophenyl)imidazol-4(5//)-one (144 R = Me). The 4-methoxyphenyl derivative and the parent phenyl derivative react similarly, as do compounds in which variation of the 2-substitutent (R = Pr , Ph, 4-O2NC6H4) was made. The mechanism of the cyclization probably involves initial formation of the anion of the alkanamide (145), which adds to the carbonyl group of the benzamido moiety to yield the tetrahedral oxyanion (146) proton transfer and dehydration then yield the heterocycle (144). The kinetics of hydrolysis in water at 70 °C and pH 2-11 of A-glycidylmorpholine (147) have been reported. ... 

CH4, and H2 while minor products such as HCCCN, H2C=CHCN, C2H4 and C4H2 were also detected. Ab initio chemical calculations revealed that the pyrolysis of acetonitrile is initiated by CH bond fission, forming a cyanomethyl radical. Products such as HCCN and H2C=CHCN have been shown to arise from the decomposition of succinonitrile, that forms by the recombination of two cyanomethyl radicals. The kinetics of thermocyclization of 2,3-diethynylquinoxaline (109) (Bergman cyclization) have been studied in various solvents. Non-polar solvents give shorter half-lives and better yields. The cyclization rates observed were found to be solvent dependent. ... 

The competitive kinetics of Scheme 3.1 can also be applied to calibrate the unimolecular radical reactions provided that kn is a known rate constant. In particular the reaction of primary alkyl radicals with (Mc3Si)3SiH has been used to obtain kinetic data for some important unimolecular reactions such as the p-elimination of octanethiyl radical from 12 (Reaction 3.5) [12], the ring expansion of radical 13 (Reaction 3.6) [8] and the S-endo-trig cyclization of radical 14 (Reaction 3.7) [13]. The relative Arrhenius expressions shown below for the... 

The kinetics of these reactions in comparison with those for methylenecyclo-propane analogs of compounds 160 have been studied by following the progress at pressures up to 3 kbar by on-line FT-IR spectroscopy [129]. The rate-enhancing influence of the additional strain in 160 overcompensates the expected retarding effect of the increased steric shielding by the second cyclopropane unit in 1 compared to methylenecyclopropane, and the cyclization rates for compounds 160 were faster by a factor of 6.8 to 8.1 in comparison with the corresponding methylenecyclopropane derivatives. 

Quinolones are obtained in the Conrad-Limpach-Knorr synthesis, which is subject to either kinetic or thermodynamic control, when aniline is reacted with a 3-keto ester (Scheme 3.11a). At room temperature the more reactive keto group combines with the aniline nitrogen atom, leading to an enamino ester the kinetic product. Cyclization of this product to a 4-quinolone requires heating at 250 C. 

The kinetics and thermodynamics of the ketalization of dihydroxyketones 145 have been examined (Equation 12) <1997T11179> the major aim of the study was to better understand these kinds of cyclizations for the synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of the zaragozic acids 147. 

Cyclization of A-acyl-oc-amino acids under acidic reaction conditions is sometimes problematic due to the difficulty in separation of the desired oxazolone from by-products while avoiding decomposition of the reactive oxazolone. This finding is particularly true in the case of 2-phenyl-5(47i)-oxazolone, an interesting compound that is a very useful intermediate to prepare a variety of novel products. The use of carbodiimides as dehydrating agents has been described as a means to improve the results. In particular, treatment of an A-acyl-a-amino acid with A-cyclohexyl-A -2-(A-methylmorpholinio)ethylcarbodiimide p-toluensulfo-nate (Scheme 7.25) is especially useful as a general synthesis of the desired saturated 5(47i)-oxazolones 101 in excellent yields.This same carbodiimide was used to study the kinetics of the formation of saturated 5(47i)-oxazolones from N-protected dipeptides... 

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