Elimination reactions conformational effects

Syn elimination and the syn-anti dichotomy have also been found in open-chain systems, though to a lesser extent than in medium-ring compounds. For example, in the conversion of 3-hexyl-4-d-trimethylammonium ion to 3-hexene with potassium ec-butoxide, 67% of the reaction followed the syn-anti dichotomy. In general syn elimination in open-chain systems is only important in cases where certain types of steric effect are present. One such type is compounds in which substituents are found on both the P and the y carbons (the unprimed letter refers to the branch in which the elimination takes place). The factors that cause these results are not completely understood, but the following conformational effects have been proposed as a partial explanation. The two anti- and two syn-periplanar conformations are, for a quaternary ammonium salt ... 

Ito T, Shinohara H, Hatta H, Nishimoto S-l (1999) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers product and laser flash photolysis studies on the oxidative splitting mechanism. J Phys Chem A 103 8413-8420 ItoT, Shinohara H, Hatta H, Fujita S-l, Nishimoto S-l (2000) Radiation-induced and photosensitized splitting of C5-C5 -linked dihydrothymine dimers. 2. Conformational effects on the reductive splitting mechanism. J Phys Chem A 104 2886-2893 ItoT, Shinohara H, Hatta H, Nishimoto S-l (2002) Stereoisomeric C5-C5 -linked dehydrothymine dimers produced by radiolytic one-electron reduction of thymine derivatives in anoxic solution structural characteristics in reference to cyclobutane photodimers. J Org Chem 64 5100-5108 Jagannadham V, Steenken S (1984) One-electron reduction of nitrobenzenes by a-hydroxyalkyl radicals via addition/elimination. An example of an organic inner-sphere electron-transfer reaction. J Am Chem Soc 106 6542-6551... 

The review covers in systematic form the literature data on the thermal decomposition of aliphatic nitrocompounds amassed over the past 25 years. Molecular structure effects on the rate and mechanism of gas phase reactions, transition state structures of bond dissociation and HNO2 elimination, the main features of decomposition in condensed phase, the data on C—N bond energy and its dependence from electronic, steric and conformational effects are considered. 

The chromophoric pyridoxal phosphate coenzyme provides a useful spectrophotometric probe of catalytic events and of conformational changes that occur at the pyridoxal phosphate site of the P subunit and of the aiPi complex. Tryptophan synthase belongs to a class of pyridoxal phosphate enzymes that catalyze /3-replacement and / -elimination reactions.3 The reactions proceed through a series of pyridoxal phosphate-substrate intermediates (Fig. 7.6) that have characteristic spectral properties. Steady-state and rapid kinetic studies of the P subunit and of the aiPi complex in solution have demonstrated the formation and disappearance of these intermediates.73-90 Fig. 7.7 illustrates the use of rapid-scanning stopped-flow UV-visible spectroscopy to investigate the effects of single amino acid substitutions in the a subunit on the rate of reactions of L-serine at the active site of the P subunit.89 Formation of enzyme-substrate intermediates has also been observed with the 012P2 complex in the crystalline state.91 ... 

An alternative elimination in solution, i.e., nitrile formation from the 2,4-dimethoxy-syn-benzaldoxime pseudosaccharyl ether was found to be first order.43 The modest influence of the solvent on the rate of reaction was interpreted254 in terms of its stabilizing effect on an all planar conformation.14 If the mechanism is similar to type (ii) a coplanar transition state would be suited for an intramolecular elimination reaction. 

Alkenes are formed by the thermal decomposition of esters, xanthates, amine oxides, sulfoxides, and selenoxides that contain at least one (3-hydrogen atom. These elimination reactions require a cw-configuration of the eliminated group and hydrogen and proceed by a concerted process. If more than one (3-hydrogen is present, mixtures of alkenes are generally formed. Since these reactions proceed via cyclic transition states, conformational effects play an important role in determining the composition of the alkene product. 

Elimination Reactions and Cyclohexane Conformation The Deuterium Isotope Effect 420 The El Reaction 421... 

RSSF spectroscopy has also been used to study the effect of active site mutations on the 3-elimination reaction catalyzed by tryptophanase. In many PLP-de-pendent enzymes, the Lys residue that forms the E(Ain) with the cofactor is preceded by a basic residue in the primary amino acid sequence. Phillips et al. (106) have examined the effect of changing Lys 269 to Arg on the formation and accumulation of reaction intermediates. The activity of the mutant enzyme is only 1096 of the native enzyme. Secondly, the mutant enzyme exhibits an altered pH dependence both in the spectrum of the native enzyme and in the catalytic rate profile. RSSF studies of the reaction of/.-alanine, z-Trp, S-methyl-z-cysteine, S-benzyl-z-cysteine (SBC), and oxindolyl-/-alanine show that all these various substrates react with the enzyme to form covalent intermediates. However, the rate and extent of quinonoid accumulation is greatly reduced. Analysis of quinonoid bands formed in the reactions of SBC and oxindolyl-z-alanine with tryptophanase show that mutation effects the equilibrium distribution of intermediates, but does not perturb either the band shape or the A x of the observed quinonoid intermediates. Therefore, the structure of the quinonoid intermediate and the surrounding active site environment are similar to the wild-type enzyme. SWSF characterization of these reactions show that the Keq for E(Aex) formation with each substrate is similar to that found for the wild-type enzyme. Instead, the primary effect of the Lys 269 Arg mutation is at the catalytic step in which the a-proton is removed from E(Aex) to form a quinonoid. These studies show that Lys 269 is not a critical catalytic residue nevertheless it does contribute to the conformational and/or electrostatic environment of the active site that is necessary for the formation and breakdown of quinonoidal species. 

Abstract This chapter emphasises on the important aspects of steric and stereo-electronic effects and their control on the conformational and reactivity profiles. The conformational effects in ethane, butane, cyclohexane, variously substituted cyclohexanes, and cis- and tra/ ,v-decalin systems allow a thorough understanding. Application of these effects to E2 and ElcB reactions followed by anomeric effect and mutarotation is discussed. The conformational effects in acetal-forming processes and their reactivity profile, carbonyl oxygen exchange in esters, and hydrolysis of orthoesters have been discussed. The application of anomeric effect in 1,4-elimination reactions, including the preservation of the geometry of the newly created double bond, is elaborated. Finally, a brief discussion on the conformational profile of thioacetals and azaacetals is presented. 

Keywords Conformational profile Steric effect E2 reaction Elcb reaction Anomeric effect Mutarotation Acetal hydrolysis Acetal formation Carbonyl oxygen exchange in esters Ozonation of acetals Orthoester and hydrolysis Numerical value of anomeric effect Relative energy of acetals 1,4-elimination Mono and dithoacetals Mono and diazaacetals... 

Many examples of stereoelectronic effects have been proposed in numerous areas of organic chemistry. The textbook example is perhaps the requirement for the anti conformation of the electrons of the scissile C—H bond with the leaving group in the E2 elimination reaction. However, over the past decade, the term stereoelectronic effect has become synonymous with an effect otherwise termed the kinetic anomeric effect or the antiperiplanar lone-pair hypothesis. While it is quite erroneous to label this hypothesis as the stereoelectronic effect , the fact that this situation has come about does serve to emphasize the ascendency of this hypothesis in the minds of many organic chemists. 

Although this is the only chapter in which stereoelectronics appears in the title, you will soon recognize the similarity between the ideas we cover here and concepts like the stereospecificity of E2 elimination reactions (Chapter 17) and the effect of orbital overlap on NMR coupling constants (Chapter 18). We will also use orbital alignment to explain the Karplus relationship (Chapter 32), the Felkin-Anh transition state (Chapter 33), and the conformational requirements for rearrangement and fragmentation reactions (Chapter 36). 

As we discussed previously, in Mechanism 1 the steric effects determined the relative reaction rates during the 5yn-elimination step a more crowded eclipsed conformation leads to a slower elimination reaction. Thus, one would expect that 1,2-dibromodecane 12 should be a very reactive substrate, (minimal steric interactions in the eclipsed conformation of the salt 14). Instead, 11 reacts 330 times faster, despite the more crowded eclipsed conformation of the salt 13 during the elimination step (Scheme 29.8). 

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