Halogen atoms, addition-elimination reactions

Et3B is an effective tool for halogen atom transfer radical reactions (see also Chap. 1.5). Perfluoroalkyl iodide [29], a-halo nitrile and a-halo ester [30] added to alkenes and alkynes at low temperature. Not only terminal alkenes but also internal alkenes can be employed to furnish iodine atom transfer adducts (Scheme 23). Furthermore, addition of perfluoroalkyl iodide to silyl and germyl enolate provided a-perfluoroalkyl ketones [31]. The reaction would involve the elimination of a tri-... 

The effect of the halogen atom on the first step of the addition-elimination reaction reflects the stability of the cyclohexadienyl anion intermediate. The electronegativity of the halogen atom explains the order of reactivity of the halogen compounds. Fluorine is the most electronegative halogen, and it is most effective in stabilizing the cyclohexadienyl anion by inductive electron withdrawal. 

From the viewpoint of the reaction mechanism, the emphasis in Scheme 5 is focused on products with the general formula R3MCH2CHB1CH2CCI3 (M = Ge, Sn) with a halogen atom in a /3-position to the element M (the so-called normal addition product). These compounds are believed to be unstable and to decompose with the elimination of an R3M radical. The phenomenon is referred to as /S-decomposition or /3-cleavage (Scheme 5). The mechanism presented in this scheme lacks the radical pair stages, while the experimental results47,48 demonstrate CIDNP effects observed for the initial compounds and the main reaction products of the interaction of R3MCH2CH=CH2 with CChBr (Table 6). Thus Scheme 5, which is based on the analysis of the reaction products, needs to be refined. 

Hydrogen abstraction from CHXO may also occur by reaction with another halogen atom (equation 38). The barrier for abstraction of hydrogen from CHFO by fluorine (Y = F) is 1.6 kcalmol"1, whereas that for abstraction of chlorine is 3.2 kcal mol"1. Addition (equation 39) of halogen Y may also occur as a competing process, followed by either a-elimination of HX (equation 40) or dissciation (equation 41) of a weaker CX bond54,55. 

Hydrogen attached to ring carbon atoms of neutral azines, and especially azinium cations, is acidic and can be replaced by a metal formally being removed as a proton. Alkyllithiums can be used as bases for this purpose however, the reaction can be accompanied by addition of the alkyl anion to the ring C=N bond. To avoid this, sterically hindered bases with strong basicity but low nucleophilicity can be utilized. Among these are lithium tetramethylpiperidide (LiTMP) and lithium diisopropylamide (LDA). If the anion contains an ortho halogen atom, then this can be eliminated to form a pyridyne (see Section 3.2.3.10.1). 

As with other aromatic substitutions, the substitution step itself can be considered to involve an approximately sps hybridization at the carbon atom under attack (10). In the idealized substitution process shown in Eq. (16), 10 may constitute either an intermediate or a transition state. If proton loss ensues directly, the process is properly called a substitution. In other situations the intermediate 10 may become allied with a radical or an anion, leading thereby to a covalent adduct 11. The final substituted product 12 may then be formed either by the elimination of H—Z (first H, then Z) or by the reversal to 10, followed by proton loss. The first case is a classical example of an addition-elimination halogenation, where the adduct is an essential species in the process. In the second case, structure 10 is a common intermediate for both the substitution and the addition reactions. Being merely a diversion of 10, the addition product is not essential to the substitution. In consequence of this, the isolation of adduct 11 may not mean that addition-elimination is the principal pathway of substitution reversal to 10 may be faster than the elimination of H—Z ( 2, k3>ki). On the other hand, the mere failure to detect adduct 11 does not rule out an addition-elimination process, for dehydrohalogenation of adduct 11 may be much faster than its formation (ki>klt k2). 

In addition, the hydrated electron acts as a nucleophile, especially with organic molecules that contain halogen atoms (Eq. 6-16). This reaction results in rapid elimination of a halide ion from the initially formed negatively charged organic species. The reaction of Eq. 6-16 is of special interest for the degradation of per-halogenated saturated hydrocarbons that are usually not affected by hydroxyl radicals (Sun et al, 2000). 

In unsaturated aliphatic systems the most important reactions are those of czirbonyl compounds of the type —COX, in which X is a good leaving group such as halogen. In general, most displacement reactions of anionic nucleophiles on the carbonyl carbon atom of acyl halides involve an addition-elimination mechanism " (e.g. equation 16). In such reactions bond-formation is in advance of bond-rupture... 

This mechanism is quite general for this substitution reaction in transition metal hydride-carbonyl complexes [52]. It is also known for intramolecular oxidative addition of a C-H bond [53], heterobimetallic elimination of methane [54], insertion of olefins [55], silylenes [56], and CO [57] into M-H bonds, extmsion of CO from metal-formyl complexes [11] and coenzyme B12- dependent rearrangements [58]. Likewise, the reduction of alkyl halides by metal hydrides often proceeds according to the ATC mechanism with both H-atom and halogen-atom transfer in the propagation steps [4, 53]. 

Such a reaction would involve addition of the halogen atom to the y-carbon atom of the allyl alcohol, a simultaneous shift of the double bond and elimination of a molecule of sulfur dioxide. The sequence is similar to what must occur when sodiomalonic ester reacts with ethylvinyl-carbinyl chloride (X) to give XI. (See p. 92.)... 

When halocyclopropanes react with an alkali metal alkoxide in an organic solvent, elimination-addition reactions take place and result in formation of alkoxycyclopropanes. In most cases the overall reaction can be regarded as a simple substitution of a halogen atom by an alkoxy group (see Section 5.2.1.1.11.2.2.), but in some cases a double substitution is observed. The latter reaction occurred when 6,6-dichloro-3-thiabicyclo[3.1.0]hexane was treated with potassium fcr/-butoxide and gave l-tcrt-butoxy-e r/o-6-chloro-3-thiabicyclo[3.1.0]hexane (1) in 68% yield. The reaction is believed to take place via a strained cyclopropene intermediate, which is trapped by nucleophilic attack of the ferr-butoxide or by reaction with furan if present.Other 1,1-dichlorocyclopropanes react analogously under similar conditions, 22-724 jjyj jien an excess of base is used, a second elimination-addition... 

When a side chain also contains a halogen atom, such as in l,l-dichloro-2-(chloromethyl)cy-clopropane (22) or 2-(bromomethyl)-l,l-dichlorocyclopropane, elimination can occur to give a methylenecyclopropane followed by two elimination-addition cycles. The elimination-addition products are accompanied by variable amounts of substitution products in which the two chlorine atoms on the ring remain intact. Thus, for example, reaction of 22 with phenolate under phase-transfer conditions gives 10% of the substitution product 24 along with 73.5% of the double-addition product, 2-methylene-l,l-bis(phenoxy)cyclopropane (23). Bulkier nucleophiles, such as those derived from 2-phenylpropanenitrile and diphenylacetonitrile, do not add twice to the same carbon atom and give 88 and 46% yield of the 2,3-bisadducts 25, respectively. 

In addition to undergoing nucleophilic substitution reactions, alkyl halides undergo J8-elimination reactions The halogen is removed from one carbon and a proton is removed from an adjacent carbon. A double bond is formed between the two carbons from which the atoms are eliminated. Therefore, the product of an elimination reaction is an alkene. Removal of a proton and a halide ion is called dehydrohalogenation. There are two important jS-elimination reactions, El and E2. 

These amidines have been extensively applied to dehydrohalogenation in organic synthesis and in some cases DBU (1) is more effective than DBN (2) [5]. A double bond can be also introduced into organic molecules by elimination of sulfonate ester instead of the halogen atom (i.e. dehydrosulfonation in addition to dehydrohalogenation). Furthermore, these amidines can be applied to the Wittig reaction [6], aldol condensation [6], 1,3-allyl rearrangement [7] and epimerization of the (3-lactam skeleton (at Ce of the penicillic acid derivatives). Sterically hindered phenols (e.g. 2,6-di(ferf-butyl)-4-fluorophenol) are (9-acetylated with DBU (1), which is superior to sodium hydroxide in the synthesis [8]. 

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