Base-catalysed elimination reactions

The mechanisms of base-induced beta-eliminations leading to alkynes are highly dependent on the type of base employed, and for this reason the dehydrohalogenations induced by metal alkoxides are considered separately from those initiated by metal amides or metal alkyls. 

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Kluger and Brandi (1986b) also studied the decarboxylation and base-catalysed elimination reactions of lactylthiamin, the adduct of pyruvate and thiamin (Scheme 2). These reactions are nonenzymic models for reactions of the intermediates formed during the reaction catalysed by the enzyme pyruvate decarboxylase. The secondary j3-deuterium KIE for the decarboxylation was found to be 1.09 at pH 3.8 in 0.5 mol dm-3 sodium acetate at 25°C. In the less polar medium, 38% ethanolic aqueous sodium acetate, chosen to mimic the nonpolar reactive site in the enzyme, the reaction is significantly faster but the KIE was, within experimental error, identical to the KIE found in water. This clearly demonstrates that the stabilization of the transition state by hyperconjugation is unaffected by the change in solvent. 

Conversion of a Mannich base hydrochloride into an a,/ -unsaturated carbonyl compound, is illustrated by the formation of phenyl vinyl ketone, which is obtained directly by steam distillation (Expt 6.147). Alternatively the Mannich base may be treated with methyl iodide to form the quaternary salt, which then gives the a,/ -unsaturated carbonyl compound by a base-catalysed elimination reaction. 

Base-catalysed elimination reactions of oxaziridines produce aldehydes or ketones together with unstable N-unsubstituted imines. Recently this reaction has been used as a synthesis method for a range of more stable N-unsubstituted ketimines thus (355) with Me COK in THF at room temperature gives (356) (90 )2", Perfluoro compound (357) has been found to undergo facile cycloaddition reactions with F2C CFC1 and acetone to yield (358) and (359) respectively2-. ... 

A number of unexplained factors warrant mention. Orientation of elimination differs for secondary and tertiary structures. The peculiar predominance of cis- rather than /ra/ii-olefin may arise from the relative stabilities of the proton-olefin complexes. but a more certain conclusion would be possible if the stereochemistry of the dehydration in the acyclic series had been determined. Assumption of the anti stereospecificity known to be favoured by the cyclohexyl systems may be unsound especially in the light of the recent stereochemical findings in base-catalysed elimination reactions (Section 2..1.1(e)). The solution of the problem of the cis/trans ratios may lie in the duality of mechanism, namely the syn-clinallanti complexity. Certainly recent results on the dehydration of threo- and eo t/iro-2-methyl-4-deutero-3-pentanols on thoria show syn-clinal rather than anti stereospecificity as indicated by deuterium analysis of the cis- and /rn/iJ-4-methyl-2-pentenes, but in these cases the trans isomer was formed in a three-fold excess over the m-olefin . Of course, the dehydration reactions on the less acidic thoria may not be good models for alumina but a knowledge of stereochemistry in the acyclic series might prove an invaluable aid in the elucidation of the mechanism. There is obviously plenty of scope for future kinetic investigations which at the moment sadly lag behind preparative studies. 

The theory of the variable transition state for base-catalysed E2 reactions has been reviewed and has been used to explain the Hammett reaction con-stants , kinetic isotope effects " , and orientational features " of some base-catalysed elimination reactions (c/. Section 2.2). 

Reactions of Sulphones.—The first report of pyrolytic elimination of aryl-sulphinic acid from an aryl alkyl sulphone has appeared, for 2-pentyl compounds these give pent-l-ene in constant proportion with cis- and t/ /i5-pent-2-ene, with exceptions for mesityl and p-nitrophenyl 2-pentyl sulphones. Base-catalysed elimination reactions leading to vinyl sulphones are well known, amine-promoted elimination from PhSOzCHa CHF-SPh following a jy/i-stereospecific course through an Elcb mechanism involving ion-pairs. A mild decarbomethoxylative elimination is the last step in a synthesis of ( )-versimide (131). ... 

Protected aldono-1,4- or -1,5-lactones [e.g. (316)] reacted with ethyl isocyano-acetate and base in an aprotic medium to give either a-(formylamino)acrylic ester derivatives [e.g. (317)] or, where base-catalysed elimination reactions can be suppressed, acyclic oxazole derivatives [e.g. (318)]. ... 

Keto-aldehydes (164) were selectively converted to non-conjugated alkynyl ketones (165) possessing an unsubstituted alkyne terminus using the one-pot nonaflation with perfluorobutane-l-sulfonyl fluoride (166) as a base catalysing elimination reaction sequences (Scheme 45). ... 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

Oxidation of sulphonamides in the presence of bromide or iodide ions and sodium methoxide in methanol also leads to formation of the N-halogeno intermediate. The nitrogen-halogen bond in these intermediates is weak and will undergo themiolysis. At -10 °C, reaction proceeds by base catalysed elimination of hydrogen halide and ftirther steps lead to an a-amino acetal 20. The reaction is carried out in an undivided cell and renders a-aminoacetals readily available for the iso-... 

Retinol Derivatives. Aryl sulphones have been used in two new syntheses in the vitamin A series. Reaction of /8-cyclocitryl phenyl sulphone (102) with the bromo-compound (103) gives the intermediate sulphone (104), which on base-catalysed elimination affords methyl retinoate (98). Alternatively retinol (99) has been prepared in high yield by condensation of the C15 bromide (105) with the C5 hydroxy-sulphone (106), followed by elimination of sulphinic acid. The syntheses... 

Ketenes are normally prepared by the base-catalysed elimination of HC1 from an acid chloride 9 or by elimination of chlorine from a chloroalkyl acid chloride with zinc dust, often assisted by ultrasound. For reactions with nucleophiles, the solution would already contain the nucleophile before the ketene 6 was generated. 

It should also be noted that base catalysed elimination could also occur by the abstraction of a hydron from the methyl group. However, the E2 reaction leads predominately to afford the thermodynamically more stable product, i.e., that with the higher substituted double bond. 

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

The mechanism of the reaction that forms diazomethane is shown below. The key step is base-catalysed elimination, though the curly arrows we have to draw to represent this are rather tortuous ... 

Steroidal primary amines have been transformed into the corresponding ketones by the action of hypochlorite and aqueous alkali. The reaction is probably analogous to the oxidation of secondary alcohols by hypohalite (p. 34) an intermediate iV-chloroamine (i) undergoes base-catalysed elimination to give the imine 2) which is hydrolysed by the aqueous medium to give the ketone. The process is illustrated for a 17 -aminoandrostane, derived by Beckmann rearrangement of the oxime of a 20-oxopregnane derivative [31]. 

Many more carbenes can be made safely from diazoalkanes if the diazoalkane is just an intermediate in the reaction and not the starting material. Good starting materials for these reactions are tosylhydrazones, which produce transient diazo compoimds by base-catalysed elimination of toluenesulfinate. The diazo compound is not normally isolated, and decomposes to the carbene on heating. 

Sulfamide (136) can be prepared by reaction of sulfuryl chloride (128) with excess ammonia in dichloromethane at -50°C, followed by extraction of the product with acetonitrile (Scheme 55). By using primary amines in the condensation, the method can be extended to obtain N,N -disubstituted sulfamides (137) (Scheme 55). A valuable route to di- and trisubstituted sulfamides involves the reaction of catechol sulfate (138) with aniline. Aniline reacts slowly with (138) to give the sulfamoyl ester (139). The unreacted aniline then promotes base-catalysed elimination of catechol to form the transient, highly reactive N-phenylsulfonylimine (140) which is trapped by aniline to yield N,N -diphenylsulfamide (141). By reaction of the ester (139) with an alkylamine, the procedure can be used to obtain trisubstituted sulfamides (142) (Scheme 56). In general, the amination of the 2-hydroxyphenyl sulfamate esters using alkylamines is an efficient route for the synthesis of trialkylsulfamides (143) (Scheme 57). 

Draw the Hammett plots for the base-catalysed elimination (/ oh) for the dissociation of the conjugate acids of the benzimidates map p values for the overall reaction. The formation of benzonitrile from benzimidate has a p value of-1.7 you will need to estimate the p value for the dissociation of the neutral imidate. 

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