Benzylic brominations, aromatic compounds

SIDE-CHAIN BROMINATION OF AROMATIC COMPOUNDS Benzylic bromination of arenes... 

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. 

Side-Chain Chlorination of Arylalkanes. Alkyl-substituted aromatic compounds can easily be halogenated at the benzylic position with chlorine or bromine.107 108,142 143 a-Monohaloalkylaromatics are usually the main products with both reagents. 

T-Stoff was a mixture of brominated aromatics including xylyl bromide, xylylene bromide and benzyl bromide. All these compounds are extreme irritants capable of severely limiting the effectiveness of unprotected troops. 

The nucleophilicity of the aromatic system can alternatively be increased by using organometallic aromatic compounds, which also solves the problem of regioselectivity. This method was applied by Sulikowski et al., who reacted a variety of sugar lactones with aryl lithiums to afford intermediate lactols which were subsequently reduced to the C-glycosides by cyanoboro hydride [137]. For example, selective orfho-bromination of monobenzylated napthalene diol 174 affords the bromide 175 which is converted into the dianion with three equivalents of n-BuLi. Treatment with the benzylated lactone 176 afforded lactol 177 (Scheme 45, the D-dideoxygluconolactone 176 was erroneously drawn as the... 

Side-chain halogenated aromatic compounds irritate the mucous membranes and are sensitive to moisture. They are not very stable thermally — the less so the less aromatic the nucleus. A simple method for determination of side-chain bromine is based on the mobility of the bromine in benzyl bromides 384... 

Benzylic Bromination of Aromatic Compounds. An efficient and fast microwave-assisted method for the preparation of benzylic bromides has appeared The 2-trimethylsilylethyl substituent on the benzenoid ring of 3 undergoes benzylic bromination followed by elimination of MesSiBr and addition of bromine to produce the dibromo compound (4) (eq 31). The ketone (5) is also observed from the hydrolysis of (4). ... 

Solid State and Related Reactions. The area of solid/solid organic reactions has been explored. " Results on the solid state nuclear bromination of aromatic compounds with NBS as well as some theoretical insights into the mechanism of the reaction have been reported. NBS on a solid support has been used to sythesize benzylic bromides under neutral conditions and for the functionalization of a-oxoaldehyde-supported silicas. ... 

The Fukuyama synthesis commenced with the copper-catalyzed asymmetric reduction of butenolide 26 to give lactone 27 in 98% enantiomeric excess (Scheme 9). Sequential alkylation with CbzCl followed by methyl acrylate provided lactone 28 and installed both of the required contiguous stereocenters. The key Curtius rearrangement was performed by conversion of the benzyl ester to the acyl azide followed by heating. Subsequent treatment with aqueous HCI provided cyclized lactam 8. This compound was then dibromi-nated to lactam 29 using bromine, ZnCl2, and formic acid, which were the only conditions that were able to introduce the orf/to-bromine. The fully elaborated aromatic compound 29 was treated with methylamine followed by PDC to obtain cyclic A -methylimide 23. 

Free-radical bromination of the following compound introduces bromine primarily at the benzylic position next to the aromatic ring. If the reaction stops at the monobromination stage, two stereoisomers result. 

The amide N-H may also be halogenated, oxidized and nitrosated. A -Bromosuccinimide (NBS), like a number of other iV-halo compounds, readily undergoes a radical fission to give a bromine radical. This provides a useful reagent for radical bromination at, for example, allylic or benzylic positions. In the presence of acid, NBS is also a mild source of the halonium ion, which is used for the addition of hypobromous acid (Scheme 3.74) to alkenes or for the bromination of reactive aromatic rings. 

The reactivity of aromatic side-chain compounds toward brominating agents is also influenced by the nature of the solvent. Under comparable conditions, the percentage formation of benzyl bromide from bronnne and toluene in various solvents is as follows ... 

We have already seen in this chapter that we can substitute bromine and chlorine for hydrogen atoms on the benzene ring of toluene and other alkylaromatic compounds using electrophilic aromatic substitution reactions. We can also substitute bromine and chlorine for hydrogen atoms on the benzylic carbons of alkyl side chains by radical reactions in the presence of heat, light, or a radical initiator like a peroxide, as we first saw in Chapter 10, (Section 10.9). This is made possible by the special stability of the benzylic radical intermediate (Section 15.12A). For example, benzylic chlorination of toluene takes place in the gas phase at 400-600 °C or in the presence of UV light, as shown here. Multiple substitutions occur with an excess of chlorine. 

We have already seen that we can substitute bromine and chlorine for hydrogen atoms on the ring of tolnene and other alkylaromatic compounds using electrophilic aromatic substitution reactions. Chlorine and bromine can also be made to replace hydrogen atoms that are on a benzylic carbon, such as the methyl group of toluene. 

The very small secondary isotope effect arising from replacement cf p-CHs by p-CDs is instructive largely because it shows that full development of carbonium ion character is not necessarily associated with a substantial benzylic deuterium secondary isotope effect. It must be recalled in this connection that the Hammett rho for Ki value is —4.410 and that the effect of one p-methyl group on the equilibrium corresponds to a typical cr+ value, i.e., the reaction is quite sensitive to stabilization of charge and p-methyl shows enhanced participation in stabilization. The observed effect is consistent with the analogous very small effects which have been observed in aromatic substitution (105), including bromination, for which p is —12, but smaller than those which have been reported for solvolyses of benzylic (106) and benzhydryl (107) compounds. It does not appear to be possible to draw a general conclusion from these data. 

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