Reaction brominations

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

Vilsmeier-Haack and Friedel-Crafts reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

As mentioned in an earlier section (cf. Chapter 1, Section III), allylic positions are subject to attack by free radicals resulting in the formation of stable allyl radicals. A-Bromosuccinimide (NBS) in the presence of free-radical initiators liberates bromine radicals and initiates a chain reaction bromination sequence by the abstraction of allylic or benzylic hydrogens. Since NBS is also conveniently handled, and since it is unreactive toward a variety of other functional groups, it is usually the reagent of choice for allylic or benzylic brominations (7). 

In this reaction, bromine has been oxidized and chlorine has been reduced, but the sodium ions remain unchanged as Na+. 

Oda et al. recently reported the synthesis of the highly strained trimeric meta-PAM 139 (Scheme 32) [82]. The required triene 140 was prepared from a,m-dial-dehyde 141 by an intramolecular McMurry coupling reaction. Bromination/dehy-drobromination of 140 furnished 139 as moderately stable, colorless crystals which decomposed above 180°C. The greater degree of strain in 139 compared to... 

SN2 reaction bromination of a primary alcohol + NaBr + I/2H2SO4... 

Bromination data became accessible over a large reactivity range when it became possible to follow low bromine concentrations. All the modern kinetic techniques are based on the fact that, since bromination is a second- or third-order reaction, bromination half-lives of a few milliseconds to several seconds can be obtained by working at very low reagent concentrations. For example, second-order rate constants as high as 109 m 1 s 1 can be readily measured if the reagent concentrations are 10-9m, the half-life of the bromine-olefin mixture then being 1 s. 

The 5-unsubstituted-l,2,3-triazol-4-ones (176, R = H) participate in electrophilic substitution reactions. Bromination in chloroform of anhydro-4-hydroxy-l,3-dimethyl-1,2,3-triazolium hydroxide (180) gave its 5-bromo derivative (182). The meso-ionic 3-aryl-1,2,3-triazol-4-ones (176, R = Me, R = Ar, R = H) gave 5-bromo derivatives (176, R = Me, R = Ar, R = Br) with bromine in acetic acid. Their reaction with sulphur monochloride gave the sulfide (189, X = S), and with thionyl chloride they gave the sulfoxide (189, X = SO). ... 

It is obvious that in these reactions bromine and iodine may be used instead of chlorine. 

Bromomethylhenzene or henzylhromide can he subjected to further nucleophilic reactions. Bromine can be replaced by a variety of nucleophiles by means of an Sn2 and SnI reaction, resulting in various monosubstituted benzenes. 

It is clear that the mechanism in Scheme 25 parallels (at least from the qualitative point of view) the mechanism of the addition of bromine to olefins shown in Scheme 11. Kinetic investigations indicate that the oxymercuration reaction involves a series of fast equilibria until the mercuronium ion (53) is formed. The subsequent nucleophilic attack of the solvent is probably the rate-limiting step, as indicated by steric requirements in bulky alkenes111. In the bromine addition, the formation of the bromonium ion is the rate-limiting step (or the rate-limiting equilibrium). However, the olefin reactivities in both reactions (bromination and oxymercuration) are identical when steric effects in the TS of the two addition reactions are taken into account110. 

The direct introduction of bromine into the allylic position of an alkene using ZV-bromosuccinimide is known as the Wohl-Ziegler reaction. Bromination is carried out in anhydrous reagents (to avoid hydrolysis of the bromoimide), usually boiling carbon tetrachloride or chloroform solution. The progress of the reaction can be followed by the fact that at first the dense N-bromosuccinimide is at the bottom of the flask and is gradually replaced by succinimide, which rises... 

The correlations for the extensively studied halogenation reactions, bromination, and chlorination are shown in Figs. 11 and 12, respectively. The excellence of these correlations extending over reactivity factors of over 1012 for bromination and 1011 for chlorination is a good test of the application of the cr+-constants to substitution reactions. Several of the values for log ( / H) or cr+ are uncertain. This uncertainty... 

Relative rates of substitution for a number of substituted thiophenes sufficient to test the applicability of po+ relationships are available for seven reactions bromination by molecular bromine, chlorination by molecular chlorine, protodetritiation, proto-dedeuteriation, acetoxymercuration, tin tetrachloride-catalyzed acetylation, and trifluoroacetylation. The relevant data are assembled in Table XXIII. 

The dibromide itself is usually prepared from the same alkene and so the reaction is not particularly useful for the synthesis of alkenes. It is useful, however, in protection strategy. During a lengthy synthesis, it may be necessary to protect a double bond so that it does not undergo any undesired reactions. Bromine can be added to form the dibromide and removed later by denomination in order to restore the functional group. 

Fig. (2). The cyclization of enone (9), gives origin of two Cyclized products (10) and (11). Ketone (10), Ketone (10) is converted to the saturated ketone (14)under standard organic reactions.Bromination and dehydrobromination of ketone (14) yields the a,P-unsaturated ketone (IS), which on subjection to catalytic hydrogenation affords (16) and this on reduction, produces alcohol (17). The compound (13) yields (18) by standard reactions that are used for the transformation of (12) to (16). Reduction with metal hydride followed by oxidation affords ketone (11), which is converted to alcohol (17)...

We started this chapter by comparing phenols with enols (Ph-enol is the phenyl enol) and now we return to them and look at electrophilic substitution in full detail. You will find that the reaction is much easier than it was with benzene itself because phenols are like enols and the same reactions (bromination, nitration, sulfonations, and Friedel-Crafts reactions) occur more easily. There is a new question too the positions round the phenol ring are no longer equivalent—where does substitution take place ... 

Just as bromine chloride is a more reactive electrophile than iodine chloride so one would expect bromine azide acting as an electrophile to be more reactive than iodine azide. In fact in solvents suitable for heterolytic reaction, bromine azide adds to chalcone less readily than iodine azide ° and this further indicates an Adj mechanism. The evidence is strengthened by the occurrence of acid catalysis of the bromine azide addition. 

---