Bromobenzene with lithium

A side-chain acyl chloride cyclizes on to a neighbouring thiol group (formed in situ by demethylation of a methylthio ether) under mild conditions. The corresponding thiopyran-4-one is obtained by the reaction of a 2-mercaptobenzoate ester and bromobenzene with lithium -isopropylcyclohexylamide (LICA) at low temperature. 

An example of the Sn2 rate dependence on the nature of the counterion is given by the reaction of -butyl 4-bromobenzene sulfonate with lithium- and tetra-n-butylammonium halides in the weakly dissociating solvent acetone (cr = 20.6) [279]. 

Explosive reaction with bromobenzene, carbon + lithium tetrachloroaluminate + sulfinyl chloride, diazomethane. Forms very friction- and impact-sensidve explosive mixtures with halogens (e.g., bromine, iodine (above 200°C)), halocarbons (e.g., bromoform, carbon tetrabromide, carbon tetrachloride, carbon tetraiodide, chloroform, dichloromethane, diiodomethane, fluorotrichloromethane, tetrachloroethydene, trichloroethylene, 1,1,2-trichloro-trifluoroethane). 

Reduction of aryl bromides with lithium aluminum hydride takes place in tetrahydrofuran solutions at room temperature. It has also been performed with bener results in the presence of di-r-butyl peroxide under UV irradiation or in the presence of titanium tetrachloride (equations 56 and 57). Reduction of bromobenzene with sodium bis(methoxyethoxy)aluminum hydride (Red-Al, Vitride) at 100-115 C gives benzene in 53% yield (Table 4). ... 

When ultrasonihcation (US) is applied to the reaction of a bromobenzene with t-butyl isocyanate and butyl lithium in diethyl ether or THF, a considerable improvement in time and yield is obtained addition of DMF at a low temperature induces cyclization [3184a). The use of ultrasonihcation in organic chemistry has been reviewed [B-58, 3615, 3646]. 

Large isotope effects were found by Roberts and co-workers (1956) for bromobenzene-2-d in the reaction with potassium amide in ammonia = 5-5) and for the reactions of chloro- and bromo-benzene-2-d with lithium diethylamide in ether = 5-7 and 5 6 respec-... 

An ethereal soln. of Fe-pentacarbonyl added slowly at -40° to a stirred soln. of phenyllithium prepared from bromobenzene and lithium, stirring continued 3 hrs., benzyl bromide in ether added, kept 2 hrs. at -40°, benzene added, and stirred with slow warming to 50° benzyl phenyl ketone. Y 57%. F. e. s. Y. Sawa, M. Ryang, and S. Tsutsumi, Tetrah. Let. 1969, 5189. 

Bromobenzene (15.7 g, 0.1 mol), together with lithium metal (0.76 g, 0.11 mol), is placed with freshly distilled THF (25 mL) in a 100-mL conical flask fitted with a reflux condenser. The flask is immersed to a depth of 2 cm in the water of a sonic cleaning bath. The bath is switched on and the reaction is essentially complete after 2 h. 

This mechanism has been confirmed using isotopically labelled fluorobenzene. Benzynes have been trapped by dienes in Diels-Alder reactions. They can also be generated by strong bases such as sodium amide in liquid ammonia in this way bromobenzene can be used without the interference of metal-halogen exchange which is the preferred course with lithium alkyls. 

It subsequently became clear that the substitution reaction could be carried out even if no other substituents were present on the aromatic ring and that even less vigorous conditions could be used. As shown in Equation 7.63, bromobenzene (CeHsBr) on treatment with lithium diethylamide (A,A-diethylaminolithium [LiN(CH2CH3)2]) in A,A-diethylamine (A-ethyl-ethanamine [(CH3CH2)2NH]) solvent results in substitution of the A,A-diethylamino group for the bromine. 

Phenylsodium, which can be made continuously in one variation of this reaction has several attractions as a phenylating agent relative to phenyl-lithium or phenylmagnesium bromide, since both chlorobenzene and sodium are cheap (compared with bromobenzene and lithium) and Grignard reagents also need expensive solvents. 

In a modified preparation of phenyllithium, bromobenzene was added to finely powdered lithium (rather than coarse particles) in ether. The reaction appeared to be proceeding normally, but after about 30 min it became very vigorous and accelerated to explosion. It was thought that the powdered metal may have been partially coated with oxide or nitride which abraded during stirring, exposing a lot of fresh metal surface on the powdered metal. 

While a current of dry nitrogen is passed through the apparatus, 400 cc. of dry ether and 6.9 g. (1 gram atom) of lithium (in small pieces) (Note 1) are placed in a 1-1. three-necked flask fitted with a dropping funnel, mechanical stirrer, and reflux condenser protected from moisture. The. stirrer is started, and 10-15 cc. of a solution of 79 g. (0.5 mole) of dry bromobenzene in 100 cc. of dry ether is added from the dropping funnel. The reaction usually starts immediately if not, the flask may be warmed, and the remainder of the mixture is then added at such a rate that the ether refluxes gently. The mixture is stirred until the lithium disappears (Note 2). 

Successful lithiation of aryl halides—carbocyclic or heterocyclic—with alkyUithiums is, however, the exception rather than the rule. The instability of ortholithiated carbocyclic aryl halides towards benzyne formation is always a limiting feature of their use, and aryl bromides and iodides undergo halogen-metal exchange in preference to deprotonation. Lithium amide bases avoid the second of these problems, but work well only with aryl halides benefitting from some additional acidifying feature. Chlorobenzene and bromobenzene can be lithiated with moderate yield and selectivity by LDA or LiTMP at -75 or -100 °C . 

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