Bromotoluenes, substituted

The substitution reaction of toluene with Br2 can, in principle, lead to the formation of three isomeric bromotoluene products. In practice, however, only o- and jp-bromotoluene are formed in substantial amounts. The meta isomer is not formed. Draw the structures of the three possible carbocation intermediates (Problem 15.48), and explain why ortho and para products predominate over meta. 

P 3] This protocol was performed identically with [P 2], with the exception of the reactants and conditions. a-Bromotoluene was nucleophilically substituted in benzene to give a-fhiocyanotoluene at 70 °C (12 h) using rhodanide coupled to a porous polymer resin [3]. 

Azide Substitutions Investigated in Micro Reactors Organis synthesis 6 [OS 6] Azide substitution of a-bromotoluene... 

The following materials were used in the preparation of the various silanes. The magnesium turnings and anhydrous diethylether were supplied by Fisher Scientific. Bromobenzene and the substituted bromobenzenes, p-bromochloro-benzene, p-bromotrifluoromethylbenzene, p-bromotoluene and p-bromoanisole, were supplied by Aldrich Chemical Co. and used as provided after the purity was checked by GC analysis. The diethoxydimethylsilane was supplied by Petrarch Systems. 

Because the rate of substitution varies with position, in a benzene derivative it is more informative and frequently more useful to talk about partial rate factors than about relative rates. A partial rate factor is defined as the rate at one particular position in the benzene derivative relative to the rate of substitution at one position in benzene. Let us, for example, calculate the para and meta partial rate factors (pf and mf, respectively) for bromination of toluene with bromine in aqueous acetic acid. Toluene brominates 605 times faster than benzene under these conditions. The product is 66.8 percent p-, 0.3 percent m-, and 32.9 percent o-bromotoluene. Attack at the para position of toluene occurs 0.668 x 605 times as fast as attack at all six positions of benzene but (0.668 x 605 x 6 = 2420) times as fast as at one position of benzene. Therefore pfCH for bromination of toluene under these conditions is 2420. There are only three times as many total carbons in benzene as meta carbons in toluene. Therefore mfca3 = 0.003 x 605 x 3 = 5.5. The definitions of the partial rate factors for monosubstituted benzenes (—R) are given in Equations 7.78-7.80. 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

For the synthesis of orfbo-bromotoluene we use a sulphonic acid. o-Bromotoluene could be synthesised by bromination of toluene or by Friedel-Crafts alkylation of bromobenzene (Fig. T). However, the reaction would also give the para substitution product and this is more likely if the electrophile is hindered from approaching the ortho position by unfavourable steric interactions. Alternatively we can substitute a group at the para position before carrying out the bromination. 

The reaction of o-, m- and/ -bromotoluenes with Bu3SnLi in THF gave the substitution product. However, cme-substitution products were found with /7-chloro- and />-fluoro-toluenes, indicating that a benzyne mechanism operates. In the presence of Li metal, the yield of the ipso substitution products increased. These results suggest that the reaction, at least partially, occurs by a radical mechanism218. 

Thus, whereas Ph3Sn ions do not react in the dark with/7-chloro- and/7-bromotoluenes, /7-dichlorobenzene, 1-chloronaphthalene and 2-chloroquinoline, showing that there is no HME reaction, good yields of substitution products (62-80%) were obtained under irradiation (equation 114). 

One of the characteristics of reactions involving benzyne intermediates is that the nucleophile can bond to the same carbon to which the leaving group was bonded, or it can bond to the carbon adjacent to the one to which the leaving group was bonded. This often results in the formation of isomeric products when substituted aromatic halides are used. For example, the reaction of yo-bromotoluene with sodium dimethyl-amide in dimethylamine as the solvent gives a 50 50 mixture of the meta and para... 

Among benzene derivatives, halogen-substituted compounds have been extensively studied and in the structure-reactivity studies " carried out on the reaction of OH and SO with the ortho and meta isomers of dichloro and dibromobenzenes and mono-bromotoluenes, the formation of substituted hydroxycyclohexadienyl radical was observed to be the major reaction channel. The bimolecular rate constants obtained for the reaction of OH with substituted halobenzenes are in the range (1.7 to 9.3) x 10 dm mol s. The rate constants obtained are found to follow the Hammett relationship for the reaction of OH with substituted halobenzenes and the p was found to be -0.5, indicating that OH radicals react by addition to the benzene ting. 

The extinction coefficient for the OH adducts of w-bromotoluene (5200 dm mol cm ) is higher than that observed for its rm-isomer (3700 dm mol" cm ). The red shift in ortho- and w to-substituted isomeric OH adducts was attributed to the stabilization of their excited states because the unpaired spin, especially in the OH adducts of isomers, is delocalized on both -Cl and -CHj substituents and they are therefore, relatively more stable than the isomers. ... 

Stevens and Bisacchi have carefully examined the trailing of benzynes, generated fiom a number of aryl bromides and sodium amide in THF, with 1,1-dimethylethylene and report procedures which afford 6 6% yields of 1,1-dimethoxycyclobutenes, e.g. (131). These compounds are hydrolyzed quantitatively to the corresponding benzocyclobutenones (132). Excellent regioselectivity was obtained with unsym-metrical benzynes derived from methoxy substituted bromobenzenes due to the polarized nature of the benzyne intermediate. Steric effects also influence regioselectivity o-bromotoluene afforded a 3 1 mixture of 3-methyl- and 6-methyl-benzocyclobutene. 

Catalysts generated from A-heterocyclic carbenes 23-25 (Figure 7) have been shown to efficiently catalyze the coupling of aryl and heteroaryl halides with indoles. Reactions conducted with the terf-butoxide base, which is typically used for the C—N coupling, did not occur, but reactions with NaOH as base occurred to high conversion85. Although 4-bromotoluene and bromobenzene reacted with numerous substituted indoles under these conditions, electron-rich and orf/zo-substituted aryl bromides reacted slowly and in low or moderate yields. 

Bromination of Alkylaromatics in SC-CO2. Product Yields. The bromination of toluene in SC-CO2 proceeded smoothly as indicated in equation 6. The major reaction product, formed in >70% yield, was benzyl bromide accompanied by a small amount (10 - 20%) of / -bromotoluene (resulting from a competing electrophilic aromatic substitution process). 

Very strong bases such as sodium or potassium amide react readily with aryl halides, even those without electron-withdrawing substituents, to give products of nucleophilic substitution by the base. Substitution does not occur exclusively at the carbon with the halide, as shown for the following reaction of (9-bromotoluene with sodium amide. 

The intermediacy of benzyne in the elimination-addition mechanism for aryl halides accounts for the regioselectivity observed in the substitution reactions of labeled chlorobenzene and 6>-bromotoluene because both can give only a single aryne intermediate. Attack at either of the aryne carbons gives rise to the products. 

---