Alpha elimination reaction

Beta-elimination reactions have been observed in a number of proteins. This reaction occurs primarily at alkaline pH conditions. Abstraction of the hydrogen atom from the alpha-carbon of a cysteine, serine, threonine, phenylalanine, or lysine residue leads to racemization or loss of part of the side chain and the formation of dehydroalanine (26). 

Alpha (a) carbon (Sections 8.1, 19.2B) In an elimination reaction, the carbon that is bonded to the leaving group. In a carbonyl com-pxjund, the carbon that is bonded to the carbonyl carbon. 

Anti-cancer drugs such as cyclophosphamide (15), aniline mustard, and nitrosoureas are transformed to reactive metabolites which are the toxic species required for their anti-cancer activity. Experiments with selectively deuterated analogs of these drugs has distinguished which pathway, among several alternative pathways of metabolism, is responsible for antitumor activity. For example, a deuterium isotope effect was observed for the formation of 4-ketocyclophosphamide (16), formed by the oxidation of the carbon alpha to the phosphoramide nitrogen, but there was no Isotope effect on the anti-tumor activity. However, there was a marked effect on the subsequent -elimination reaction and consequent decrease in anti-tumor activity by deuterium substitution at C-5. Thus, the formation of acrolein and phosphoramide mustard is rate determining for the anti-tumor activity of cyclophosphamide. 

If the carbanion reacts with acetophenone, 2-hydroxy-2-phenyl-propyl phenyl ketone is formed. This compound is not stable in alkaline solution because the hydrogens alpha to the carbonyl and the hydroxy are acidic. This 3-hydroxy carbonyl compound can undergo an elimination reaction to form a more stable 3 unsaturated compound. The reaction steps are shown below ... 

The initial product of elimination is a highly electron-deficient species, usually a carbene or a nitrene, which subsequently reacts rapidly to give products. The base-catalysed hydrolysis of chloroform is an alpha-elimination . The properties of the electron-deficient species represent a rapidly expanding field of organic chemistry and this subject is discussed in the following chapter. In this chapter, only apparent alpha-eliminations, (e.g. reaction (5)), are included. The nature of the products indicates the intermediacy of electron-deficient species, but kinetic studies show the processes occur via reactions of the precursor carbanions, viz. 

In concentrated methanolic solutions of sodium methoxide, due to a shortage of base-solvating solvent molecules, the activity of methoxide as measured by H- rises more rapidly than methoxide concentration . The rate of me-thanolysis of chloroform (log bJ, an ElcB-alpha-elimination, is proportional to the H- value of the medium, which is not surprising as the reaction is under thermodynamic control. Observed rate coefficients (log/t jj ) for the E2 reactions of 2-phenylethyl chloride and l-chloro-3,3-dimethylbutane, which are under kinetic control, show a much slower response to medium changes and in fact increase linearly with methoxide concentration . 

These examples of the carbanion mechanism based on substrates possessing alpha sulphone groups would be more certain if founded on kinetic evidence. In all the cases quoted above, the enhanced reactivity of the sulphones relative to the other model compounds may be explicable in terms of beta hydrogen activation and a normal concerted elimination reaction. 

The above conclusion must be remembered when considering carbon isotope effects for elimination reactions. Certainly the alpha- and beta-carbon isotope effects for elimination from propyl trimethylammonium ion indicate a different extent of rehybridisation at the two carbon atoms in the transition state, but a more definite conclusion requires additional kinetic evidence. 

Rappoport has presented a detailed outline of the mechanisms of the reactions of vinyl halides with nucleophilic reagents. Modena et /. " have provided further evidence in support of a spectrum of transition states for elimination from activated vinyl halides induced by alkoxide bases. Cristol and Whittemore have shown that the stereoselectivity of elimination from vinyl halides is largely determined by the choice of basic reagent alkoxide bases encourage am/-elimination, whereas syn-elimination and alpha-elimination become dominant with lithium alkyls. 

Abstraction reactions are elimination reactions in which the coordination number of the metal does not change. In general, they involve removal of a substituent from a ligand by the action of an external reagent, such as a Lewis acid. Two types of abstractions, a and /3, are illustrated in Figure 14.16 they involve removal of substituents from the a and /3 positions (with respect to the metal), respectively, of ligands. Alpha abstraction is used to synthesize carbyne complexes (Section 13.6.3). 

The mechanism of the reaction (see Eq. 3.10) is believed to involve initial coordination of the electrophilic carbene to the nitrogen lone pair. The zwitterion thus formed undergoes proton transfer from nitrogen to carbon yielding an N-substituted aminodichloromethane. Base catalyzed beta-elimination of the elements of HQ followed by alpha-elimination of another mole of HCl yields the desired isonitrile. 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

The use of this direct oxide reduction process is replacing fluoride reduction as it eliminates neutron exposure to operating personnel (alpha particles from plutonium decay have sufficient energy to eject neutrons from fluorine by the a,n reaction) and eliminates reduction residues which require subsequent recovery. 

The first evidence that an elimination-addition mechanism could be important in nucleophilic substitution reactions of alkanesulfonyl derivatives was provided by the observation (Truce et al., 1964 Truce and Campbell, 1966 King and Durst, 1964, 1965) that when alkanesulfonyl chlorides RCH2S02C1 were treated in the presence of an alcohol R OD with a tertiary amine (usually Et3N) the product was a sulfonate ester RCHDS020R with exactly one atom of deuterium on the carbon alpha to the sulfonyl group. Had the ester been formed by a base-catalysed direct substitution reaction of R OD with the sulfonyl chloride there would have been no deuterium at the er-position. Had the deuterium been incorporated by a separate exchange reaction, either of the sulfonyl chloride before its reaction to form the ester, or of the ester subsequent to its formation, then the amount of deuterium incorporated would not have been uniformly one atom of D per molecule. The observed results are only consistent with the elimination-addition mechanism involving a sulfene intermediate shown in (201). Subsequent kinetic studies... 

The core of the crystalline region of irradiated PE contains residual free radicals. These diffuse slowly to the interface with the amorphous region, where, in the presence of dissolved oxygen, whose equilibrium concentration is maintained by diffusion, they initiate an autooxidative chain of degradation.89 Postirradiation annealing in an inert atmosphere at a temperature above the alpha-transition temperature (85°C) leads to a rapid mutual reactions of the free radicals and eliminates the problem.90... 

The simplified mechanism which accounts for this phenomenon is that the very high-energy radiation is able to abstract atoms from molecules, which then become unsaturated and can react further. This phenomenon was first reported in 1924 by Lind and Bardwell (L13), who bombarded simple saturated hydrocarbons up to and including butane with alpha particles. They found that hydrogen and methane in a ratio of 5 to 1 were eliminated to give higher hydrocarbons, up to those heavy enough to be liquids and solids. Low yields of condensates are obtained for these endothermic reactions. 

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