Bromide elimination

FIGURE 8.11 When a Lewis base reacts with an alkyl halide, either substitution or elimination can occur. Substitution (Sn2) occurs when the Lewis base acts as a nucleophile and attacks carbon to displace bromide. Elimination (E2) occurs when the Lewis base abstracts a proton from the p carbon. The alkyl halide shown is isopropyl bromide, and elimination (E2) predominates over substitution with alkox-ide bases. 

Halo-l-benzothiepins 4 can be synthesized by the treatment of 7a-halobenzo[fe]cyclopropa-[e]thiopyran-7-ols 2 with hydrogen bromide and subsequent hydrogen bromide elimination from the 2,4-dihalo-2,3-dihydro-l-benzothiepins 3 by l,5-diazabicyclo[4.3.0]non-5-ene (DBN).9 The alcohols 2 are prepared by Grignard reaction of the corresponding 7a-halobenzo[ft]cyclopropa[c]thiopyran-7-ones l18 and are used for the synthesis without purification. The intermediate dihalodihydro-l-benzothiepins 3 are not isolated due to their thermal lability related and more stable compounds are described in Section 2.1.2.1. 

The chemical meaning of these mathematical equations is that the rate law is first order with respect to the amine base for each reaction (i.e. interconversion of la and Ih and hydrogen bromide elimination). 

The fact that the rate law of hydrogen bromide elimination is first order with respect to the base may be interpreted by an E2 mechanism. The antiperiplanar position of the hydrogen and the bromine atoms in Ih also makes this mechanism very likely. Earlier the same mechanism was proposed for the elimination reaction of some tertiary a-halo ketones (ref. 19). Other mechanism, such as ElcB or El, seems to be very improbable considering the lack of any deuteration at C-2 or the lack of any rearrangement and the fact that the generation of a-keto cations requires acidic conditions (ref. 20). 

The above section already introduced the influence of leaving groups at the benzylic position that eliminate to form and regenerate QM3, and the trend extends beyond adducts formed by the deoxynucleosides as expected. The standard benzylic acetate of QMP4 eliminates completely from the deprotected phenol under neutral aqueous conditions and ambient temperature within approximately 20 h, while an equivalent benzyl bromide eliminates completely within 5 min.48 Benzylic phosphates are also extremely labile, and, if the phosphate backbone of DNA is able to trap QM, the resulting products are likely to be too labile for standard detection.53,54 In contrast, amines and thiols are much less susceptible to elimination from the benzylic position and require forcing conditions to regenerate the parent QM.26,30 The benzylic alcohol derivative also appears stable under almost all thermal conditions and only eliminates routinely to form a QM after photochemical excitation.55... 

Some related reactions are worth mentioning in this context. Addition of allylnickel bromide to styrene oxide to give an alcohol has been reported (example 7, Table IV). Tsutsumi has described the Darzens-type reaction of two molecules of a-bromoketones to give dimethylfurans (example 8, Table IV). This reaction consists of the addition of the ketomethylenic group to the carbonyl group of another molecule, followed by epoxide formation and bromide elimination. A subsequent rearrangement leads to a dialkylfuran. 

Bromoethylamine (11.133, R = Br, Fig. 11.18) is a potent nephrotoxin used to create an experimental model of nephropathy. Its mechanism of toxicity is postulated to involve perturbation of mitochondrial function, and its metabolism was investigated in a search for toxic metabolites. In rat plasma, 2-bromoethylamine was converted to aziridine (11.134), formed by intramolecular nucleophilic substitution and bromide elimination [155], Another major metabolite was oxazolidin-2-one (11.136). This peculiar metabolite resulted from the reaction of 2-bromoethylamine with endogenous carbonate to form carbamic acid 11.135, followed by cyclization-elimination to oxazoli-din-2-one. In aqueous media containing excess carbonate, the formation of... 

The appearance of turbidity indicates saturation of alkyl halide. In this way both sodium thiosulfate and 2-bromopropane are nearly in a one-phase system, thus shortening significantly the heating period. Furthermore, the competitive hydrogen bromide elimination and the ensuing acid-promoted decomposition of thiosulfate into sulfur and sulfur dioxide are minimized, the checkers added 300 ml. of water over a period of 90 minutes. 

This procedure illustrates a recently published, simple, general method for the synthesis of conjugated dienes from olefins. The scope of the reaction is shown in Table I.5 In most of these examples hydrogen bromide. .elimination can be effected by stirring a solution of the olefin-bromo-methanesulfonyl bromide adduct in methylene chloride with one equivalent of triethylamine at room temperature. Only two equivalents of the more costly potassium tert-butoxide are then needed in the second elimination step the yields using the two-base procedure are generally superior to that obtained using only potassium tert-butoxide. 

You met a stereospecific elimination in Chapter 19. The requirement for the H and the Br to be anti-periplanar in the E2 transition state meant that the two diastereo isomers of this alkyl bromide eliminated to alkenes with different double bond geometries (p. 491). 

The fluorine containing 7t-exTTF 550 was obtained in the 1,3-dipolar cycloaddition of DMAD to dithiocarboxylic moiety of the dithiocrotonate 549 and subsequent reaction of the resulting intermediate ylide with the starting 549 as a Michael acceptor in an addition-elimination process followed by ethyl bromide elimination. Formation of the second 1,3-dithiole moiety in 550 was connected with the consecutive cycloaddition followed by ethyl bromide elimination (Equation 71) <2003CEJ4324>. 

The Payne rearrangement is cited on p. 79, Eq. 114, Ref. 739. Fully substituted fluorooxiranes have been prepared from an a-haloketone with a Grignard reagent followed by hydrogen bromide elimination (Eq. 59). ... 

For the hydrogen bromide elimination an E2 mechanism was considered, as tetra-O-acetyl-a-D-mannopyranosyl bromide and tri-O-acetyl-a-o-rhamno-pyranosyl bromide, which contain the bromine atom and 2-acetoxy group in the trans positions, could not be dehydrobrominated. 

Under similar conditions, hydrogen bromide elimination occurred only from the (Z)-isomer of l-bromo-3-[(3-methoxyphenyl)oxy]propene (171) to give acetylene 172 (82JOC2484). 

Benzo[c]cinnoline is a weak base with a of 2.2 in water and 1.6 in 50% aqueous ethanol.Cryoscopic measurements show that it is dipro-tonated to some extent in 100% sulfuric acid. Well-defined quaternary salts result from heating benzo[c]cinnoline with alkyl halides and sul-fates. These are reported to decompose on treatment with ammonia, regenerating benzo[c]cinnoline, but apparently nucleophilic displacements of halogen by amines have been carried out on certain highly substituted examples in the synthesis of cationic dyestuffs. Quaternizations of benzo[c]cinnoline with a,a)-dibromo-propane and -butane are accompanied by hydrogen bromide elimination to give the cyclic iminium salts 40 and 41. When 40 is dehydrogenated, or merely refluxed in ethanol. 

Only one of these bromides eliminates to give alkene A. Why Neither alkene eliminates to give alkene B. Why not ... 

Dehydrogenation of aromatic aldoximes to nitrile oxides [1, 80, before references]. N-Bromosuccinimide in dimethylformamide is an excellent reagent for the dehydrogenation of aromatic aldoximes to the corresponding nitrile oxides.17 Triethylamine serves well as base required to bind the hydrogen bromide eliminated since it is... 

To prepare the (24f )-2p,3p-epoxidc 40 the A2-6-keto acetonide 57 was transformed with N-bromosuccinimide (NBS) in dimethoxyethane (DME) to the bromohydrin 62. Acid deprotection to 63 followed by hydrogen bromide elimination with sodium methoxide led to the desired compound 40. 

Where functionalization is required adjacent to the site of direct bromination, it is sometimes possible to move the halide through hydrogen bromide elimination... 

Modification of base and solvent can also induce a change from Saytzeff to Hofmann orientation even in alkyl bromide eliminations . In one unimolecu-lar elimination , the least substituted olefin is formed predominantly - ", but in this case it is the thermodynamically more stable product by about 1.8 kcal.mole, due to eclipsing between the /-butyl and methyl substituents in the more substituted olefin , and consequently the Saytzeff pattern is not violated (115). 

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