Haloalkanes elimination

Just as addition of HX to an alkene produces haloalkanes, elimination of HX from a haloalkane by reaction with a strong base, such as potassium ethoxide, produces an alkene ... 

We recall that S 2 reactions are most effective with primary haloalkanes. Elimination reactions decrease the yield for secondary haloalkanes. 

Both phase transfer and crown ether catalysis have been used to promote a-elimination reactions of chloroform and other haloalkanes.153 The carbene can be trapped by alkenes to form dichlorocyclopropanes. 

Step 1 is fundamentally an SN2 reaction (kinetics related to structural variations of the reactants,16 8 retention of stereochemistry at phosphorus912), except in those instances wherein a particularly stable carbocation is produced from the haloalkane component.13 A critical experiment concerned with verification of the Sn2 character of Step 1 by inversion of configuration at the carbon from which the leaving group is displaced was inconclusive because elimination rather than substitution occurred with the chiral secondary haloalkane used.14 An alternative experiment suggested by us in our prior review using a chiral primary substrate apparently has not yet been performed.2... 

Typically, the organic substrate in these reactions is a haloalkane. Primary haloalkanes will generally give 100% substitution products, but tertiary and cyclohexyl halides usually undergo 100 % elimination, with secondary haloalkanes producing a mixture of the two. Studies of the chloride and bromide displacements of (R)-2-octyl methanesulfonate have shown that phase transfer displacements proceed with almost complete inversion of stereochemistry at the carbon centre, indicating an Sjv2-like mechanistic pathway [41],... 

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 The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59].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]. 

The dehydrohalogenation of 1- or 2-haloalkanes, in particular of l-bromo-2-phenylethane, has been studied in considerable detail [1-9]. Less active haloalkanes react only in the presence of specific quaternary ammonium salts and frequently require stoichiometric amounts of the catalyst, particularly when Triton B is used [ 1, 2]. Elimination follows zero order kinetics [7] and can take place in the absence of base, for example, styrene, equivalent in concentration to that of the added catalyst, is obtained when 1-bromo-2-phenylethane is heated at 100°C with tetra-n-butyl-ammonium bromide [8], The reaction is reversible and 1-bromo-l-phenylethane is detected at 145°C [8]. From this evidence it is postulated that the elimination follows a reverse transfer mechanism (see Chapter 1) [5]. The liquidrliquid two-phase p-elimination from 1-bromo-2-phenylethanes is low yielding and extremely slow, compared with the PEG-catalysed reaction [4]. In contrast, solid potassium hydroxide and tetra-n-butylammonium bromide in f-butanol effects a 73% conversion in 24 hours or, in the absence of a solvent, over 4 hours [3] extended reaction times lead to polymerization of the resulting styrene. 

In the formation of the carbon-to-carbon double bond, the Br atom, together with an H atom on an adjacent carbon atom, has been removed or eliminated from the haloalkane and not replaced. This reaction is often referred to as a base-induced elimination reaction (see p. 62). 

The basic OH" ion initially attacks an H atom on the carbon atom adjacent to the halogen-bearing carbon atom in the haloalkane. It forms a bond with this H atom and an HO-H molecule is generated. At the same time, the pair of electrons in the C-H bond moves between the two carbon atoms on the left-hand side of the haloalkane to form a double bond. Finally, the C-Br breaks heterolytically, releasing a Br" ion. You are not required to know this mechanism, but it helps to explain why the elimination reaction is referred to as base-induced. 

When a haloalkane with p-hydrogen atom Is heated with alcoholic solution of potassium hydroxide, there Is elimination of hydrogen atom from p-carbon and a halogen atom from the a-carbon atom. As a result, an alkene is formed as a product. Since p-hydrogen atom is involved in elimination. It Is often called p-elimination. 

Further stereochemical studies with di- or tri-haloalkanes corroborated the general picture of a strong dependence of the direction of elimination on the nature of the catalyst. The data in Table 12 may serve as an exam-... 

The mechanism of dehydrohalogenation of haloalkanes varies from a concerted E2 mechanism to a carbanionic ElcB mechanism, where the /j-hydrogen has been made sufficiently acidic to be removed, leaving a carbanion.4,5 The E2 mechanism of dehydrohalogenation takes place in one step. The ElcB or carbanionic mechanism of dehydrohalogenation has two steps the first step being deprotonation, and the second one elimination of the halide ion. 

The reactivity order also appears to correlate with the C-X bond energy, inasmuch as the tertiary alkyl halides both are more reactive and have weaker carbon-halogen bonds than either primary or secondary halides (see Table 4-6). In fact, elimination of HX from haloalkenes or haloarenes with relatively strong C-X bonds, such as chloroethene or chlorobenzene, is much less facile than for haloalkanes. Nonetheless, elimination does occur under the right conditions and constitutes one of the most useful general methods for the synthesis of alkynes. For example,... 

Iron(II) porphyrins react readily with haloalkanes in the presence of reducing agents, e.g., excess iron powder, to give chlorocarbene complexes 15,32). With the insecticide DDT [2,2-bis(4-chlorophenyl)-1,1,1 -trichloro-ethane, (C1C6H4)2CHCC13], the reaction proceeds one step further, by elimination of HC1 from the carbene complex, to give diarylvinylidene complexes 33) ... 

The first term, representing acid-"catalyzed" hydrolysis, is important in reactions of carboxylic acid esters but is relatively unimportant in loss of phosphate triesters and is totally absent for the halogenated alkanes and alkenes. Alkaline hydrolysis, the mechanism indicated by the third term in Equation (2), dominates degradation of pentachloroethane and 1,1,2,2-tetrachloroethane, even at pH 7. Carbon tetrachloride, TCA, 2,2-dichloropropane, and other "gem" haloalkanes hydrolyze only by the neutral mechanism (Fells and Molewyn-Hughes, 1958 Molewyn-Hughes, 1953). Monohaloalkanes show alkaline hydrolysis only in basic solutions as concentrated as 0.01-1.0 molar OH- (Mabey and Mill, 1978). In fact, the terms in Equation(2) can be even more complex both elimination and substitution pathways can operate, leading to different products, and a true unimolecular process can result from initial bond breaking in the reactant molecule. 

As has already been pointed out, the Finkelstein reaction can be conducted in situ in the absence of solvents. For example, alkylations of purine and pyrimidine bases with alkyl halides and dimethyl sulfate have been carried out by solid/liquid phase-transfer catalysis in the absence of any additional solvent [48], as have cyanation of haloalkanes [49] and / -eliminations [50]. Noteworthy is the synthesis of glycosyl isothiocyanates by the reaction of potassium thiocyanate with molten glycosyl bromide at 190 °C [51]. 

There are two types of elimination reactions, E1 and E2 reactions. The mechanism for E1 is a multistep reaction that involves the formation of a carbocation intermediate. The E2 mechanism is a series of steps, bond breaking and bond formation, that occurs simultaneously. Similar to the Sn2 case outlined above, both the haloalkane and the base are involved in the transition state. 

In the preceding paragraphs we dealt with procedures where amino groups are introduced in the last step into halo- and alkoxyacetylenes which can eventually be prepared in situ by elimination from the corresponding haloalkanes and alkenes. 

Reaction of a secondary haloalkane with a basic nucleophile yields both substitution and elimination products. This is a less satisfactory method of ether preparation. 

In Eqs. (5-23) and (5-24), there is no net change of charge after reaction, but for Eq. (5-22) charge is created and for Eq. (5-25) it is destroyed. Further examples of observed effects for solvent changes on rates of mono- and bimolecular eliminations are given by Hughes and Ingold [16, 44]. In most cases studied, haloalkanes and onium salts in ethanol/water mixtures, the observed solvent effects are in the expected direction. 

Reduced solvation of commonly used E2 bases (HO , RO ) in dipolar non-HBD solvents may elevate their reactivities to such an extent that E2 reactions of quite inert substrates occur [306]. Halide ions in dipolar non-HBD solvents are sufficiently strong bases to promote dehydrohalogenations of haloalkanes [73, 74]. Even the fluoride ion is the most efficient in this reaction [307, 308, 600] the elimination rates decrease in the order F > Cl > Br > I . 

Among the fluoride ion promoted reactions which occur in dipolar non-HBD solvents are alkylations of alcohols and ketones, esterifications, Michael additions, aldol and Knoevenagel condensations as well as eliminations for a review, see reference [600]. In particular, ionic fluorides are useful in the dehydrohalogenation of haloalkanes and haloalkenes to give alkenes and alkynes (order of reactivity R4N F > K ([18]crown-6) F > Cs F K F ). For example, tetra-n-butylammonium fluoride in AjA-dimethylformamide is an effective base for the dehydrohalogenation of 2-bromo-and 2-iodobutane under mild conditions [641] cf Eq. (5-123). 

Mochida I., Noguchi H., Fujitsu H., Seiyama T., and Takeshita K. (1977) Reactivity and selectivity in the reductive elimination of halogen from haloalkanes by chromous, cuprous, and stannous ions. Can. J. Chem. 55, 2420-2425. 

The alkynide ion can undergo alkylation with a variety of alkylating reagents, such as haloalkanes and alkyl sulfates, with the formation of a carbon-carbon bond. The alkynide ion is also strongly basic so that elimination reactions may accompany or subvert the substitution reaction. Group I metal alkynides in liquid ammonia give mainly substitution products with primary haloalkanes but secondary and tertiary haloalkanes give mainly elimination products, as do 2-substituted primary haloalkanes (equation 1). 

An elimination reaction, dehydrohalogenation, can occur for chloro-, bromo- and iodoalkanes. In such a reaction, the halogen, X, from one C atom and a hydrogen from an adjacent C atom are eliminated. A double bond between two carbon atoms is formed the molecule becomes more unsaturated. The net reaction is the transformation of an alkyl halide (or haloalkane) into an alkene. Dehydrohalogenation reactions usually require a strong base such as sodium hydroxide, NaOH. 

Dehydrohalogenation An elimination reaction in which a hydrogen halide, HX (X = Cl, Br, I), is eliminated from a haloalkane. A C=C double bond is formed. 

Elimination reactions of other two-carbon haloalkanes were studied using REX catalyst. Ethyl bromide and ethyl iodide formed ethylene and hydrogen halide in high yield at 66°. The reactions shown here also... 

A peculiai- case of phosphoryl radical addition to difluoroalkenes involves the reaction of trialkyl phosphites with l-bromo-2-iodo-l,l,2,2-tetfafluoroethane under ultraviolet irradiation (254 nm). Surprisingly, the corresponding 2-iodo-l,l,2,2-tetrafluoroethylphosphonates are formed in 42 8% yields with no detectable amount of the bromo derivative (Scheme 3.39). The proposed mechanism involves a halide-induced dealkylation of the trialkyl phosphite radical cation followed by addition of the product phosphoryl radical to tetrafluoroethene (generated by halide anion elimination) and iodide radical abstraction from the starting haloalkane. s... 

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