Halides, aryl, also chlorides, bromides

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

One of the best methods for the introduction of iodine into aromatic rings is the reaction of diazonium salts with iodide ions. Analogous reactions with chloride, bromide, and fluoride ions give poorer results, and 14-25 and 13-20 are preferred for the preparation of aryl chlorides, bromides, and fluorides. However, when other diazonium reactions are carried out in the presence of these ions, halides are usually side products. Aniline has also been converted to fluorobenzene by treatment with t-BuONO and Sip4 followed by heating. A related reaction between PhN=N—N C4Hg and iodine gave iodobenzene. ... 

Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3)4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with yym-tetramethyldisilo-xane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3SiH/Pd(OAc)2/dppp (l,3-bis(diphenylphosphino)propane) (Eq. 60).201... 

Aryl halides can also be reduced by tin hydrides76,77, although these reactions always require initiators because the stronger C—X bonds in aryl halides are less reactive than the C—X bonds in alkyl halides. In fact, a series of meta- and para-substituted bromobenzenes, where X is either meta- or para-CH3O-, C=N, Cl, F, CF3, CH3, Bu-f or 2,6-dichloro, have been reduced by tributyltin deuteride (equation 60). It is worth noting that the more reactive bromide is reduced selectively in the presence of the less reactive chloride and fluoride groups (equation 61). 

Kumada-type couplings of alkyl halides 98 with aryl Grignard reagents 99 yielding alkylarenes 100 recently received much attention (see Part 2, Sects. 2.1 and 5.1, Part 3, Sect. 2.1). A vanadium-based method was developed by Oshima and coworkers (Fig. 30) [189]. Primary and secondary alkyl bromides, iodides, and also chlorides were coupled to phenylmagnesium bromide catalyzed by 10 mol%... 

Hydrolysis of chlorobenzene and the influence of silica gel catalysts on this reaction have been studied by Freidlin and co-workers (109). Pure silica gel gave up to 45% phenol from chlorobenzene at 600°C. When the silica gel was promoted with 2% cupric chloride, up to 75% phenol was obtained (381). A number of other salts were tested by Freidlin and co-workers as promoters, but they exerted an adverse effect on the activity or selectivity of the catalyst. With 0.2% cupric chloride and 6% metallic copper, the activity of silica-gel was doubled (389). At 500° under the above conditions, the halides were hydrolyzed at rates decreasing in the following order chloride, bromide, iodide, fluoride (110). The specific activation of aryl halides by cupric chloride was demonstrated by conversion of chlorobenzene to benzene and of naphthyl chloride to naphthalene when this catalyst was supported on oxides of titanium or tin (111). The silica promoted with cupric chloride was also found to be suitable for hydrolysis of chlorophenols and dichlorobenzenes however, side reactions were too prominent in these cases (112). 

There is no difficulty in effecting Grignard reactions with aryl iodides or bromides or with primary or secondary alkyl iodides, bromides, or chlorides halides of alkylic and benzylic type also react well, but there is some difficulty with tertiary alkyl halides. 

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