Mechanics of cyclization

Even if no general conclusions can be drawn on the basis of existing material, it appears that further study of cyclization of these substances could elucidate the mechanism of cyclization of thiosemi-carbazones of a-keto acids which is of fundamental importance in the chemistry of dioxotriazines. 

The mechanism of cyclization of diaminopyrimidines by nitrous acid appears not to have been studied in detail. For the preparative procedure an aqueous solution of alkaline nitrite is treated with the diaminopyrimidine either in the form of a salt or with simultaneous addition of hydrochloric or acetic acid. The first phase of the reaction is usually carried out at 0°C, in some cases the reaction being terminated by heating to 50-60°C. With diaminopyrimidines which are sparingly soluble in water, the reaction was carried out in an organic solvent using amylnitrite. Excess nitrous acid can possibly attack the amino groups present. This was employed in some cases for the preparation of the hydroxy derivatives. ... 

If the first e step, i.e., heterogeneous electron transfer, is slow (non-Nernstian) or if the cyclization reaction is faster than the electron transfer itself, the electron transfer becomes rate-determining and nothing can be done about the mechanism of cyclization. 

Figure 11 Proposed mechanism of cyclization of dehydrated NisA by NisC. The cyclization reaction shown results in the formation of the B-ring of nisin. The possible stabilization through a /3-turn-like structure via hydrogen bonding between the amide NH of Cys and the carbonyl of Dha/Dhb is shown and may explain the high stereoselectivity observed in nonenzymatic cyclizations involving four amino acids as discussed in the text. Reprinted with permission from B. Li W. A. van der Donk, J. Biol. Chem. 2007, 282, 21169-21175.

Studies of relative rates, activation parameters, kinetic isotope, and solvent isotope effects, and correlation of rates with an acidity function, have elucidated the mechanisms of cyclization of diacetyl aromatics (23-26) promoted by tetramethyl-ammonium hydroxide in DMSO.32 Rate-determining base-catalysed enolate anion formation from (24-26) is followed by relatively rigid intramolecular nucleophilic attack and dehydration whereas the cyclization step is rate determining for (23). 

The mechanism of cyclization has been investigated several times in the past [8]. It is catalyzed by the presence of a base the first step of the reaction is, in fact, the formation of a green dihydrobilin free base. Visible light can then furnish the necessary energy for cyclization. Otherwise, once the dihydrobilin free base is formed, coordination of a metal ion achieves the correct geometry for cyclization. The metal exerts a template action in holding the reactive sites in proximity. The participation of the metal in the cyclization process is demonstrated by the fact that metal free corrole has been isolated as reaction product when Cr or Ru salts have been used, but no light was needed for the reaction to occur [24]. 

The oxidative cyclization process is analogous to the formation of a methylenedioxy group (see page 27), whilst the mechanism of cyclization is exactly the same as that invoked in formation of a tetrahydroisoquinoline ring, i.e. a Mannich-like... 

Synthetic utility for the 2+2 photocycloaddition has been a driving force for understanding the mechanism of cyclization. Stereocontrol of the 2+2 photocycloaddition allows an efficient synthesis of small ring... 

In his 1940 review Plate subjected the experimental material on dehydrocyclization of paraffins published to that time to a critical analysis (304) and concluded that aromatization of paraffins at the temperatures employed will depend upon the selection of proper catalysts in order to suppress the competing reactions, that the multiplet theory satisfactorily explains the mechanism of cyclization, and that intermediate formation of olefins is conceivable on oxide catalysts but can hardly occur on platinum. 

These developments in cationic polymerization of 1,3,5-trioxane are discussed in more detail, because in this system the problems related to the mechanism of cyclization are now well understood. Cyclic oligomers were identified, isolated, their molecular weight distribution was determined, and the plausible explanation for observed distribution was given. From the synthetic point of view, the cationic polymerization of 1,3,5-trioxane offers the possibility of preparing macrocyclic polymers with relatively narrow molecular weight distribution and predictable (within discussed limits) molecular weights. The cyclic polymers can be prepared easily in relatively large quantities and conveniently separated from linear polymer by alkaline hydrolysis of the latter. 

Chen, I.W., and Charalampous, F.C., 1967, Studies on the mechanism of cyclization of glucose 6-phosphate to D-inositol 1-phosphate. Biochim. Biophys. Acta. 136 568-570. 

The indole system has been the most extensively studied, particularly in regard to the mechanism of cyclization." It is noteworthy that in some instances an isomerization of the anilinoketone occurs, viz., R CH(NHRX OR" to R COCH(NHR)R From a preparative standpoint, the method is valuable in the formation of several indoles in excellent yields, e.g., 2,3-dimethyl indole (85%)" and 2-ethyl-3-methylindole (92%). Condensation of aniline derivatives of 2-chlorocyclohexanone yields the corresponding tetrahydrocarbazoles... 

The detailed mechanisms of cyclization in the polymerization of other monomers may be similar to this one or slightly different. For aU these sterns, however, the final equilibrium can be described by a formal schai in which a linear polymer s -ment is convated into a macrocyclic segment togetha with a correspondingly short-er, linear segment ... 

Scheme 75. A probe for distinguishing the radical and anionic mechanisms of cyclization.

Abnormal structures in polyacrylonitrile and their relation to the mechanism of cyclization... 

Fig.8 Bifunctional mechanism of cyclization from C3/C4-fragments by erionite [me metallic site ac acidic site]...

The mechanism of cyclization with ortho esters differs from that of simple acylating agents, such as acetic anhydride, in that the aromatic rather than the aliphatic primary amino group is the first site of attack. The extended conjugation that arises in this way, as in 65 for example, promotes the reaction. Ring closure is aided by the loss of the —OEt group and by its... 

Understanding and predicting the product selectivity for the [2 + 2] photocycloaddition has been a driving force for understanding the mechanism of cyclization. As will be noted in the later sections of this chapter, a majority of the regioselective and stereoselective [2 -I- 2] photocycloaddition examples can be justiHed by analysis of the mechanistic details. 

The mechanism of cyclization of the aminonitrile to the 3-arylisoquinolin-4-one involves a spiro rearrangement with both anhydrous HF and sulfuric acid [87JCR(S)36] whereby an ortho or para oxygenated substituent is involved in the initial cyclization step with subsequent bond breakage to... 

The characteristic feature in the mechanism of cyclization reactions is the reductive cascade ring closure. The mechanisms of silylcarbocyclizations (SiCaC, SiCaT,f CO-SiCaC, = CO-SiCaB, and CO-SiCaT reductive... 

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