Allyllic bromination

Pyran-2-one, 5,6-dibromo-5,6-dihydro-reactions, 3, 735 Pyran-2-one, 5,6-dihydro-allylic bromination, 3, 799 dehydrogenation, 3, 724, 799 H NMR,3, 581 synthesis, 3, 841, 843 Pyran-2-one, 4,6-dimethyl-irradiation, 3, 677 photochemistry, 3, 678 Pyran-2-one, 5,6-dimethyl-chloromethylation, 3, 680 conformation, 3, 631 Pyran-2-one, 5-f ormyl-IR Spectra, 3, 595 Pyran-2-one, 6-formyl-IR spectra, 3, 595 Pyran-2-one, 5-halo-synthesis, 3, 799 Pyran-2-one, 3-hydroxy-IR spectra, 3, 595 Pyran-2-one, 4-hydroxy-methylation, 2, 57 3, 676 pyran-4-one synthesis from, 3, 816 reactions with phosphorus oxychloride, 2, 57 synthesis, 3, 792, 794, 795, 798 tautomerism, 2, 56 3, 642 Pyran-2-one, 4-hydroxy-6-methyl-methylation, 3, 692 reactions... 

Neutral HX addition X = P, S, Se, Si Allylic bromination Carbon-halogen addition... 

The fact that the bromine concentration remains at veiy low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must... 

An important application of the allylic bromination-dehydrobromination approach is the formation of the A -diene system e.g. 110) in vitamin D synthesis. Dehydrobromination of the A -7-bromo system in the presence of mercuric chloride gives a high yield of A -diene. ... 

A"" -3-Ketones are more reactive than cross-conjugated A ""-3-ketones. A"" -3,3-CycIoethylenedioxy compounds can be easily prepared by acid-catalyzed reaction with ethylene glycol or by exchange dioxolanation. 3,3-Cycloethylenedioxy-A -dienes can be prepared from 3,3-cycloethy-lenedioxy-A -enes by allylic bromination and dehydrobromination. Acid hydrolysis yields A"" -3-ketosteroids. ... 

As we saw when discussing allylic bromination in Section 10.4, A-bromosuccin-imide (NBS) is a convenient free-radical brominating agent. Benzylic brominations with NBS are nonnally perfonned in carbon tetrachloride as the solvent in the presence of peroxides, which are added as initiators. As the exanple illustrates, free-radical bromination is selective for substitution of benzylic hydrogens. 

The allylic bromination of an olefin with NBS proceeds by a free-radical chain mechanism. The chain reaction initiated by thermal decomposition of a free-radical initiator substance that is added to the reaction mixture in small amounts. The decomposing free-radical initiator generates reactive bromine radicals by reaction with the N-bromosuccinimide. A bromine radical abstracts an allylic hydrogen atom from the olefinic subsfrate to give hydrogen bromide and an allylic radical 3 ... 

Allylic bromination of pregnenolone acetate with dibromodi-methylhydantoin affords the 7-bromo compound (155) of undefined stereochemistry. Dehydrobromination by means of collidine followed by saponification affords the 5,7 endocyclic cis,cis-diene, 156. This compound contains the same chromophore as ergosterol, a steroid used as a vitamin D precursor. The latter displays a complex series of photochemical reactions among the known products is lumisterol, in which the stereochemistry at both C9 and Cio is inverted. Indeed, irradiation of 156 proceeds to give just such a product (158). This reaction can be rationalized by... 

Preparing Alkyl Halides from Alkenes Allylic Bromination 339... 

This allylic bromination with NBS is analogous to the alkane halogenation reaction discussed in the previous section and occurs by a radical chain reaction pathway. As in alkane halogenation, Br- radical abstracts an allylic hydrogen atom of the alkene, thereby forming an allylic radical plus HBr. This allylic radical then reacts with Br2 to yield the product and a Br- radical, which cycles back... 

In addition to its effect on stability, delocalization of the unpaired electron in the allyl radical has other chemical consequences. Because the unpaired electron is delocalized over both ends of the nr orbital system, reaction with Br2 can occur at either end. As a result, allylic bromination of an unsymmetrical alkene often leads to a mixture of products. For example, bromination of 1-octene gives a mixture of 3-bromo-l-octene and l-bromo-2-octene. The two products are not formed in equal amounts, however, because the intermediate allylic radical is... 

The products of allylic bromination reactions are useful for conversion into dienes by dehydrohalogenation with base. Cyclohexene can be converted into 1,3-cyclohexadiene, for example. 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

The mechanism of benzylic bromination is similar to that discussed in Section 10.4 for allylic bromination of alkenes. Abstraction of a benzylic hydrogen atom generates an intermediate benzylic radical, which reacts with Br2 to yield product and a Br- radical that cycles back into the reaction to carry on the chain. The Br2 necessary for reaction with the benzylic radical is produced by a concurrent reaction of HBr with NBS. 

Allylic bromination, 339-340 mechanism of, 339-340 Allylic carbocation, electrostatic potential map of, 377, 489 resonance in, 488-489 SN1 reaction and, 376-377 stability of, 488-489 Allylic halide, S l reaction and. 377 S j2 reaction and, 377-378 Allylic protons, ]H NMR spectroscopy and, 457-458... 

Allylic bromination, with A -bromosuccinimide (NBS), of 4-ethoxy-l,2-dihydrocyclo-pent[rf]azepine (8), formed by ethylation (with Meerwein s reagent) of the corresponding 4-oxo derivative, followed by in situ dehydrobromination of the resulting bromo compound with basic alumina, produces a low yield of l-bromo-2-ethoxycyclopent[c/]azepine (9) as a photosensitive, sapphire-blue, crystalline solid.55... 

It is generally supported that the bromination with NBS proceeded by a radical (ref. 11) or an ionic mechanism via bromine molecule. For instance, the former was suggested in benzylic and allylic bromination with NBS for Whol-Ziegler reaction (ref. 12). Calo et al. (ref. 5) accounted NBS brominated phenol by the latter mechanism. 

The formation of alkyl shifted products H and 14 can be explained in terms of the formation of endo-intermediate 21 formed by endo attack of bromine to 2 (Scheme 4). The determined endo-configuration of the bromine atom at the bridge carbon is also in agreement with endo-attack. Endo-Intermediate 21 is probably also responsible for the formation of cyclopropane products 12 and 15. The existence of cyclopropane ring in 12 and 15 has been determined by and 13c NMR chemical shifts and especially by analysis of cyclopropane J cH coupling constants (168 and 181 Hz). On the basis of the symmetry in the molecule 12 we have distinguished easily between isomers 12 and 15. Aryl and alkyl shift products IQ, H, and 14 contain benzylic and allylic bromine atoms which can be hydrolized easily on column material. 

That the mechanism of allylic bromination is of the free-radical type was demonstrated by Dauben and McCoy, who showed that the reaction is veiy sensitive to free-radical initiators and inhibitors and indeed does not proceed at all unless at least a trace of initiator is present. Subsequent work indicated that the species that actually abstracts hydrogen from the substrate is the bromine atom. The reaction is initiated by small amounts of Br. Once it is formed, the main propagation steps are... 

The mechanism of allylic bromination by N-bromosuccini-mide (NBS, 1) (p T 198) is so often given wrongly in textbooks that the correct route is worth repeating here. NBS is usually used in refluxing carbon tetrachloride and the inltation step Is either thermolysis... 

Allylic bromination of unsymmetrical alkenes may give many products. Occasionally one product is formed in reasonable yield, e.g. (3), but this is a matter for trial and error. 

Bromide (6) is clearly needed and can be made by allylic bromination of ester (7), Crotonic acid (8) is... 

The Knoovenagol method (p T 161 ) gives high yields of crotonic acid. The allylic bromination uses N3S in CCl and the ylid (9) is stable enough to be isolated. 

With the A-ring unit readily available, we directed our attention to the formation of the B-ring. At first, we duplicated the five step scheme reported in Sih s strigol synthesis involving 1) esterification of the acid 14, 2) allylic bromination with N-bromo 8 ucc i n imi d e (NBS) to 15, 3) condensation with the sodium salt of dimethyl malonate to 16, 4) alkylation with methyl bromoacetate to 17, and 5) acid catalyzed hydrolysis and decarboxylation to the acid 18. 

Propene undergoes allylic bromination when treated with A-bromosuccinimide (NBS) in CCI4 in the presence of peroxides or light. 

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