Bromohydrins formation

FIGURE 6 13 Mechanism of bromohydrin formation from cyclopentene A bridged bromonium ion is formed and is attacked by a water molecule from the side opposite the carbon-bromine bond The bromine and the hydroxyl group are trans to each other in the product... 

We now have a new problem Where does the necessary alkene come from Alkenes are prepared from alcohols by acid-catalyzed dehydration (Section 5.9) or from alkyl halides by dehydrohalogenation (Section 5.14). Because our designated starting material is ten-butyl alcohol, we can combine its dehydration with bromohydrin formation to give the conect sequence of steps ... 

Mechanism of bromohydrin formation by reaction of an alkene with Br2 in the presence of water. Water acts as a nucleophile to react with the intermediate bromonium ion. 

In practice, few alkenes are soluble in water, and bromohydrin formation is often carried out in a solvent such as aqueous dimethyl sulfoxide, CH3SOCFI3 (DMSO), using a reagent called W-brornosuccinimide ( rBS) as a source of Br2. NBS is a stable, easily handled compound that slowly decomposes in water to yield Br2 at a controlled rate. Bromine itself can also be used... 

The anti stereospecificity of epoxidation by the peracid is interpreted as due to association of the reagent with the allylic hydroxyl group which directs the entering oxygen atom to the same face of the molecule. The stereospecificity of bromohydrin formation is explicable in terms of steric approach control involving initial attack of the bulky bromine atom on the face opposite to the benzylic hydroxyl group (7). 

Notes Used for allylic and benzylic brominations (Wohl-Zieeler Reaction). With moist DMSO the reagent is useful for bromohydrin formation, providing trans addition of bromine and water. Can brominate alpha to carbonyl in carbonyl (carboxyl)-containing compounds. With DMF useful for aromatic bromination of activated aromatic rings, such as phenols, aromatic ethers, aniline derivatives and activated heterocyclic compounds. For similar chemistry, see also NBA, N-Bromoacetamide. 

Coughlin P, Roberts S, Rush C, Willetts A (1993) Biotransformation of Alkenes by Haloperoxidases Regiospecific Bromohydrin Formation from Cinnamyl Substrates. Biotechnol Lett 15 907... 

Andersson M, Conte V, Di Furia F, Moro S (1995) Vanadium Bromoperoxidases Mimicking Systems Bromohydrins Formation as Evidence of the Occurrence of a Hypobromite-Like Vanadium Complex. Tetrahedron Lett 36 2675... 

Attack on the bromonium ion by methanol is analogous to the attack by water in the mechanism of bromohydrin formation. 

With NBS in aqueous DMSO, cyclohexene gives racemic /ra/ -2-bromo-1 -cyclohexanol. This stereochemical result means that we have a Irans-addition. In the analogous bromohydrin formation from 3,3-dimethylcyclohexene, the analogous dimethylated 2-bromo-l-cyclohexanol is also produced /ra/rv-selectively as well as regioselectively (Figure 3.43). In the bromo-nium ion intermediate, the H20 molecule does not react at the hindered neopentyl center. This is as expected from the rules for SN2 reactivity (Section 2.4.4), and results in high regioselec-tivity. 

Bromohydrin formation is usually achieved by NBS in aqueous DMSO. 

This is not important as deacylation destroys that centre anyway 32. Epoxidation followed the best route was bromohydrin formation with NBS in water followed by elimination with DBU and gave an 8 1 selectivity for epoxidation on the opposite face to the substituent 33. 

S. namaquense its structure is based on spectral study Several new syntheses of meserabrine have been reported. One uses a cinna-monitrile as a synthon, with introduction of a "formyl anion" at the S-position, followed by Robinson annelation and finally elaboration of the cyanomethyl side-chainA second employs an intramolecular ene cyclisation of an acylnitroso-olefin to a hydroxamic acid, reducible to a lactam. Then follows a series of simple steps (N-methylation, hydroxylation via bromohydrin formation, debromi-... 

For addition of HOBr the unsaturated compound is usually stirred for some hours at room temperature with bromine water, then the excess of hypobromite is removed by sodium hydrogen sulfite, the solution is saturated with salt, and the bromohydrin is shaken out of the aqueous phase into ether or CHC13. A cold solution of hypobromite obtained from bromine and alkali carbonate may be used in place of bromine water.281 The tendency of styrene to bromohydrin formation is so great that -(bromomethyl)benzyl alcohol is obtained in excellent yield even in hot water (60-90°) by use of a bromine solution in the presence of KBr.261 282... 

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