Elimination—addition dehydrohalogenation

The Dow Process utilizes an elimination/addition reaction to convert chlorobenzene to phenol. The proposed mechanism for this reaction is shown in Figure 8-3. The high-temperature reaction begins with chlorobenzene and aqueous sodium hydroxide. Note that this mechanism starts with the hydroxide attacking as a base, beginning dehydrohalogenation to form benzyne. The second hydroxide ion attacks as a nucleophile to form a carbanion intermediate, which behaves as a base in the last step to yield the final product. 

Eliminations are the opposite of additions. In an elimination one molecule loses the elements of another small molecule. Elimination reactions give us a method for preparing compounds with double and triple bonds. In Chapter 7, for example, we shall study an important elimination ealled dehydrohalogenation, a reaction that is used to prepare alkenes. In dehydrohalogenation, as the word suggests, the elements of a hydrogen halide are eliminated. An alkyl halide becomes an alkene ... 

Co(CO)4] ) dehydrohalogenation [Eq. (15)] followed by addition of HCo(CO)4, or whether splitting out of HCo(CO)4 occurs from the alkyl-cobalt [Eq. (14)], which is the malonate precursor, followed by HCo(CO)4 addition in the opposite direction. In one case [Eq. (15)], olefin formation proceeds directly from the bromide and no reversibility of any steps is required, while according to Eq. (14) olefin formation proceeds from elimination of HCo(CO)4. 

As has been mentioned previously, one is most likely to find analogies to catalytic reactions on solids with acidic and/or basic sites in noncatalytic homogeneous reactions, and therefore the application of established LFERs is safest in this field. Also the interpretation of slopes is without great difficulty and more fruitful than with other types of catalysts. The structure effects on rate have been measured most frequently on elimination reactions, that is, on dehydration of alcohols, dehydrohalogenation of alkyl halides, deamination of amines, cracking of the C—C bond, etc. Less attention has been paid to substitution, addition, and other reactions. 

Vinylation or arylation of alkenes with the aid of a palladium catalysts is known as the Heck reaction. The reaction is thought to proceed through the oxidative addition of an organic halide, RX onto a zero-valent [PdL2] species followed by coordination of the olefin, migratory insertion of R, reductive elimination of the coupled product and dehydrohalogenation of the intermediate [HPdXL2] (Scheme 6.1). 

As previously reported, the radical addition of CF2Br2 on glycals (initiated by sodium dithionite) affords difluorobromomethylated compounds. These latter molecules are easily dehydrohalogenated in the presence of TBAF. Under such conditions, these difluorovinyl compounds can add a fluoride ion (from TBAF). The subsequent elimination of the acetate moiety yields trifluoromethyl unsaturated compounds. The double bond can then be reduced (Figure 6.37). The same kind of reaction occurs in the presence of DAST with gcm-difluor-omethylene compounds, which are obtained by addition of an ylide onto an ulose (Figure 6.37). 

Azirines are also made by carbene addition to nitriles (89 — 90) and by thermal or photochemical (68JA2869) elimination of N2 from vinyl azides (e.g. 91 — 92). Vinyl azides are prepared by the Hassner reaction (68JOC2686, 71ACR9), where iodine azide is first added to an alkene and the resultant (3-iodoazide is dehydrohalogenated with base (Scheme 37) (86RTC456). 

Dehydrohalogenations at two adjacent carbon atoms lead to compounds with C = CorCsC bonds and arc an important route to fluorinated alkencs and alkynes. Some dehydrohalogenations occur spontaneously, others require elevated temperatures, and the majority occur in a basic medium which takes up the eliminated hydrogen halide.1 4 In addition to aqueous or alcoholic alkalis, organic bases such as triethylamine are often used for this purpose. 

Dehydrohalogenations have been used for the preparation of many polyfluorinated compounds containing additional functionalities. Hydrogen fluoride is eliminated from 2//-tetrafluoro-propionyl fluoride (1) to give trifluoroacryloyl fluoride (2).87... 

Kopecky s synthesis of trimethyldioxetane employed the base-mediated dehydrohalogenation of 2-methyl-2-hydroperoxy-3-bromobutane. Subsequently, this type of eliminative cyclization (14) has been applied to the preparation of scores of dioxetanes. Additionally, many dioxetanes have been prepared by the addition of singlet oxygen to electron-rich olefins which do not possess allylic hydrogens (15), a method discovered first by Bartlett and Schaap... 

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). 

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). 

Alkenes are a central functional group in oiganic chemistry. Alkenes are easily prepared by elimination reactions such as dehydrohalogenation and dehydration. Because their n bond is easily broken, they undergo many addition reactions to prepare a variety of useful compounds. 

Acetylide ion alkylation is limited to primary alkyl bromides and iodides, RCHgX, for reasons that will be discussed in detail in Chapter 11. In addition to their reactivity as nucleophiles, acetylide ions are sufficiently strong bases that they cause dehydrohalogenation instead of substitution when they react with secondary and tertiary alkyl halides. For example, reaction of bromocyclohexane with propyne anion yields the elimination product cyclohexene rather than the substitution product cyclohexylpropyne. 

Dehydrohalogenation. a-Bromobenzalacetone has been prepared from benzal-acetone by addition of bromine and elimination of HBr by reaction with sodium... 

Double dehydrohalogenations have been used recently in the synthesis of a number of bis(methylene)triangulanes (Table 5). Typically, the starting dihalides are prepared by a sequence of cyclopropanation with chloromethylcarbene and monodehydrochlorination, in which a tetrahydropyranyl ether serves as the source of the bromide or iodide moiety (see Section 5.2.2.1.1.1.). The double elimination is carried out with potassium ier/-butoxide in dimethyl sulfoxide at or near room temperature, and gives low to moderate yields of bis(methyl-ene) products. In some cases mixtures of diastereomers were obtained due to the lack of stereospecificity of the preceding carbene addition to the double bond which consequently led to the presence of a mixture in the starting material. The procedure is illustrated by the synthesis of 1,4-bis(methylene)spiropentane (2). ... 

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