Cleavage steps

A novel route to azelaic acid is based on butadiene. Butadiene is dimerized to 1,5-cyclooctadiene, which is carbonylated to the monoester in the presence of an alcohol. Hydrolysis of this ester foUowed by a caustic cleavage step produces azelaic acid in both high yield and purity (56). 

Pj release occurs at a relatively apparent slow rate (kobs = 0.005 s" ), so that the transient intermediate F-ADP-Pj in which P is non-covalently bound, has a life time of 2-3 minutes (Carlier and Pantaloni, 1986 Carlier, 1987). While the y-phosphate cleavage step is irreversible as assessed by 0 exchange studies (Carlier et al., 1987), the release of Pi is reversible. Binding of H2PO4 (Kp 10 M) causes the stabilization of actin filaments and the rate of filament growth varies linearly with the concentration of actin monomer in the presence of Pi (Carlier and Pantaloni, 1988). Therefore, Pi release appears as the elementary step responsible for the destabilization of actin-actin interactions in the filament. 

SO the product in this case is also the hydrazone, and not the azo compound. In fact, compounds of the type 16 are seldom isolable from the reaction, though this has been accomplished. The cleavage step shown is an example of 12-41 and, when a carboxyl group cleaves, of 12-38. The overall process in this case is called the Japp-Klingemann reaction and involves conversion of a ketone (17) or a carboxylic... 

In a reaction with a moderately long chain, much more of the product will be produced by abstraction (14.4) than by coupling (14.5). Cleavage steps like (14.2)... 

Figure 4.11 Optimized structures of CH cO species, as indicated, over aqueous-solvated Pt(lll) as determined by DFT in Cao et al. [2005]. Horizontal and vertical arrows indicate C—H and O—H cleavage steps, respectively. Reaction energies are included for the aqueous phase [Cao et al., 2005] and the vapor phase (in parentheses) [Desai et al., 2002]. The thermodynamically preferred aqueous phase pathway is indicated by bold arrows (in blue). (See color insert.)...

TMSI also effects rapid cleavage of esters. The cleavage step involves iodide attack on the O-silylated ester. The first products formed are trimethylsilyl esters, but these are hydrolyzed rapidly on exposure to water.96... 

Furman B, Thurmer R, Kahuza Z, Voelter W, Chmielewski M. A new acetal resin valuable for the solid-phase synthesis of 1-oxacephams via a cyclization/cleavage step. Tetrahedron Lett 1999 40 5909-5912. 

Prado-Cabrero, A., A. F. Estrada et al. (2007). Identification and biochemical characterization of a novel carotenoid oxygenase Elucidation of the cleavage step in the Fusarium carotenoid pathway. Mol. Microbiol. 64(2) 448 160. 

A prototype of a microwave reaction vessel that takes advantage of bottom filtration techniques was presented by Erdelyi and Gogoll in a more recent publication. Therein, the authors described the use of a modified reaction vessel (Fig. 7.2) for the Emrys instruments (see Section 3.5.1) with a polypropylene frit, suitable for the filtration /cleavage steps in their microwave-mediated solid-phase Sonogashira coupling (see Scheme 7.19) [21]. 

For general solid-phase reactions in a dedicated multimode instrument, an adaptable filtration unit is available from Anton Paar (see Fig. 3.18). This tool is connected to the appropriate reaction vessel by a simple screw cap and after turning over the vessel, the resin is filtered by applying a slight pressure of up to 5 bar. The resin can then be used for further reaction sequences or cleavage steps in the same reaction vessel without any material loss. However, at the time of writing, no applications of this system for solid-phase synthesis had been reported. 

For the cydative cleavage step, it turned out that aprotic conditions were definitely superior to the use of protic media. Thus, employing N,N-dimethylformamide as solvent at somewhat elevated temperatures furnished the desired compounds in high yields and excellent purities. Having established the optimized conditions, various phthalic acids and amines were employed to prepare a set of phthalimides (Scheme 7.51). However, the nature of the amine was seen to have an effect on the outcome of the reaction. Benzyl derivatives furnished somewhat lower yields, probably due to the reduced activities of these amines. Aromatic amines could not be included in the study as auto-induced ring-closure occurred during the conversion of the polymer-bound phthalic acid. 

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