Bromobenzene arylation

Ullman reaction The synthesis of diaryls by the condensation of aromatic halides with themselves or other aromatic halides, with the concomitant removal of halogens by a metal, e.g. copper powder thus bromobenzene gives diphenyl. The reaction may be extended to the preparation of diaryl ethers and diaryl thio-ethers by coupling a metal phenolate with an aryl halide. 

When allylic alcohols are used as an alkene component in the reaction with aryl halides, elimination of /3-hydrogen takes place from the oxygen-bearing carbon, and aldehydes or ketones are obtained, rather than y-arylated allylic alcohoIs[87,88]. The reaction of allyl alcohol with bromobenzene affords dihydrocinnamaldehyde. The reaction of methallyl alcohol (96) with aryl halides is a good synthetic method for dihydro-2-methylcinnamaldehyde (97). 

Another method for the hydrogenoiysis of aryl bromides and iodides is to use MeONa[696], The removal of chlorine and bromine from benzene rings is possible with MeOH under basic conditions by use of dippp as a ligand[697]. The reduction is explained by the formation of the phenylpalladium methoxide 812, which undergoes elimination of /i-hydrogen to form benzene, and MeOH is oxidized to formaldehyde. Based on this mechanistic consideration, reaction of alcohols with aryl halides has another application. For example, cyclohex-anol (813) is oxidized smoothly to cyclohexanone with bromobenzene under basic conditions[698]. 

PMMA is not affected by most inorganic solutions, mineral oils, animal oils, low concentrations of alcohols paraffins, olefins, amines, alkyl monohahdes and ahphatic hydrocarbons and higher esters, ie, >10 carbon atoms. However, PMMA is attacked by lower esters, eg, ethyl acetate, isopropyl acetate aromatic hydrocarbons, eg, benzene, toluene, xylene phenols, eg, cresol, carboHc acid aryl hahdes, eg, chlorobenzene, bromobenzene ahphatic acids, eg, butyric acid, acetic acid alkyl polyhaHdes, eg, ethylene dichloride, methylene chloride high concentrations of alcohols, eg, methanol, ethanol 2-propanol and high concentrations of alkahes and oxidizing agents. 

Certain ketones (qv) can be synthesized conveniendy from readily available aryl hahdes such as chloro- or bromobenzene (150,151). 

For the synthesis of a suitable arylboron compound, usually an aryl halide is converted to an aryllithium or aryl Grignard derivative, and then reacted with a trialkoxyborane to yield an arylboronic ester, e.g. the phenylboronic acid diisopropyl ester 13 from bromobenzene 11 ... 

Such reactions appear to be rather general in scope, since an aryl example, the substitution for bromine in bromobenzene, and for halogen in a normal alkyl halide has also been observed (21). 

The arylation of the methoxyethanol with the bromobenzene was investigated changing the nature of the base (Fig. 11), but using the bipyridylnickel catalyst, a shorter time, and keeping the same temperature. 

The alcohol can be primary or secondary the arylation with bromobenzene (Y is an hydrogen) affords quantitative yields with the primary alcohols but only 40 %, even after a longer time, with the 2-pentanol as secondary alcohol. 

By comparison of the hydrolysis rate for the chloro- and bromobenzene catalyzed with cuprous oxide (Fig. 16), it is easy to show that the reactivity of bromobenzene as arylating agent is much higher than the reactivity of chlorobenzene the yields in phenolate is higher than 90 % after half an hour at 230 °C for the bromobenzene whereas the chlorobenzene affords only about 65 % after 15 hours, even at higher temperature (250°C). 

In this way, the overall result is the arylation of the nucleophile by the bromobenzene with the enhanced reactivity of the iodobenzene. 

Tetrasubstituted phosphinous amides of the type R2NPPh2 have been successfully arylated at phosphorus by the action of bromobenzene, in a process catalyzed by NiBr2, to give the aminophosphonium bromides [R2NPPh3] Br [109]. Other representative members of this class form phosphane-borane complexes [62], are aminated at phosphorus by chloramine to yield bis(amino)phos-phonium salts [110] and have been claimed to be protonated at phosphorus by ethereal tetrafluoroboric acid, as determined by NMR analysis [111]. 

The only reported reaction of a simple aryl halide is that of bromobenzene with [Co (BAE)], which appears to be one of the most nucleophilic Co(I) complexes 46, 16). a-Iodopyridine also reacts with [Co(CN),)H] (75). 

Besides benzyl chloride, methyl- and/or chlorine-substituted benzyl chlorides, phenethyl chloride, etc. are also successfully employed to give 2 -diaralkylaminofluorans in excellent yield. However, aryl halides such as chlorobenzene and bromobenzene hardly enable the reaction, though aryl iodides such as iodobenzene give 2 -diarylaminofluorans in low yield. 

Fig. 5 Electrochemical reduction of aryl halides showing the variation of the apparent transfer coefficient with the scan rate. iodobenzene, O bromobenzene, V 1-iodonaphthalene, O 4-methyliodobenzene, at 298 K, iodobenzene at 329 K.

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). 

Abeywickrema and Beckwith162 have measured the primary hydrogen-deuterium kinetic isotope effect for the reaction between an aryl radical and tributyltin hydride. The actual isotope effect was determined by reacting tributyltin hydride and deuteride with the ort/ro-alkcnylphcnyl radical generated from 2-(3-butenyl)bromobenzene (equation 111). 

Scheme 15 shows the synthesis of an oxazole 63a and thiazole 63b derivative, accomplished by Yokooji et al. [59]. They employed arylation using tertiary phosphines and bromobenzene with CS2CO3 in xylene to form these compounds. 

Arylation of C-H bonds is achieved by coupling reactions of C-H bonds with aromatic compounds such as halides, triflates, and organometallic reagents. Early works in this field involve the reaction of aryl halides with norbornene. As shown in Scheme 5, the coupling reaction of bromobenzene with norbornene in the presence of Pd(PPh3)4 as a... 

An interesting decarbamoylative arylation is observed when the reaction of secondary 2-thiophenecarboxamides with bromobenzene is conducted in the presence of Pd(OAc)2 and a bulky phosphine [P(<9-biphenyl)(/-Bu)2] (Equation (61 )).70 However, the arylation occurs at the 2-position without the removal of the ester moiety when the reaction of 3-carboethoxyfuran with an aryl bromide is conducted.71... 

The arylation of heteroaromatic compounds is also achieved by aryl-aryl coupling reaction. The arylation of A-methylimidazole with bromobenzene occurs under palladium catalysis (Equation (62)).72 The arylation of thiazole with aryl iodide occurs at the 2-position under PdCl2(PPh3)2/CuI catalysis.73 In this case, tetrabutylammonium fluoride improves the activity of the catalyst. Alternatively, thiazoles and benzothiazole are efficiently arylated... 

Palladium-catalyzed reaction of 2-hydroxy-2-methylpropiophenone with aryl bromides shows a unique multiple arylation via successive C-C and C-H bond cleavages, giving tetraarylethanes.96 For example, the reaction of 2-hydroxy-2-methylpropiophenone with bromobenzene in the presence of Pd(OAc)2, P(/-Bu)3, and CS2CO3 gives 1,1,2,2-tetraphenylethane quantitatively, together with l,4,4-triphenyl-7-methylisochroman-3-one (13% yield) (Equation (74)). 

Miura s group carried out a heteroaryl Heck reaction of bromobenzene and 1-methylimidazole and isolated both mono-arylation (53%) and bis-arylation products [45], In accord with Ohta s observation, the first arylation took place at the electron-rich C(5) and the second arylation occurred at the more electron-poor C(2). 

It can be applied generally homologous bromobenzenes such as dibromobenzene and all possible alkyl bromides come within its scope. The reaction takes place also, although less readily, between two molecules of aryl bromide ... 

Nickel(O) triphenylphosphine can be used to couple aryl halides and alkenes to synthesize substituted olefins [149], 1,2-bis[(di-2-propylphosphino)benzene]nick-el(0) can be used to couple aryl halides [150], and l,2-bis[(diphenylphos-phino)ethane]nickel(0) can be used to prepare benzoic acid from bromobenzene in the presence of carbon dioxide [151]. 

A detailed investigation of the Ni-dppe catalyzed formation of biphenyl from bromobenzene has resulted in the proposal of a catalytic cycle (Scheme 1) in which the tr-aryl-nickel intermediate is first reduced into the corresponding ArNi then transformed into a diaryl-nickel(III) complex. This complex then undergoes a reductive elimination leading to the product and Ni, followed by the regeneration of the Ni system [32, 34],... 

Very few transition-metal catalyzed electroreductive carbon-heteroatom bond formations have been described. The electrochemical silylation of allylic acetates was carried out in the presence of Pd-PPha [131]. The electrosynthesis of arylthioethers from thiophenol and aryl halides [132] and the coupling of bromobenzene with dichlorophenylphosphine [133] were performed with Ni-bpy as catalyst. 

---