Bromination of adamantanes

Stetter and WuUf noted that boron tribromide exerts a marked catalytic effect on the bromination of adamantane and reported that under these conditions the product formed is 1,3-dibromoadamantane. However, Baughman" established that the product actually is 1-bromoadamantane. He then found that addition of a trace of aluminum bromide (tribromide) to the boron tribromide leads to the formation of 1,3-dibromoadamantane in yield of 74%. 

A 100-ml flask is charged with 25 ml of bromine and 10 g of adamantane and heated under reflux for 3 hours. The cooled mixture is dissolved in 100 ml of carbon tetrachloride, and the carbon tetrachloride solution is washed with 100-ml portions of saturated bisulfite solution until the color of bromine is discharged. The solution is then washed twice with water and dried (magnesium sulfate). The solvent is removed (rotary evaporator) and the product is recrystallized from methanol. (For best recovery of the recrystallized material, the methanol solution should be cooled in a Dry Ice cooling bath.) The product has mp 108°. 

The synthesis begins with the halogenation of adamantane (74) with bromine to give 76 or chlorine and AlClg to give 75. The four bridgehead positions... 

Nitronium tetrafluoroborate in the presence of pyridine poly(hydrogen fluoride) (PPHF) can be used to substitute chlorine or bromine in adamantanes and other hydrocarbons (see Table 21).90... 

Kinetic investigations83 into the bromination of methylidene adamantane (31) and allyl-benzene (32) reveals the importance of the assistance of the solvent to the rate-limiting ionization to form bromonium ion from the CT complex. 

Similar symmetry problems confront the substitution reactions of other systems, e.g. noradamantane, homoadamantane and ethanoadamantane. Nor-adamantane, for example, may be brominated when treated with bromine under vigorous conditions but a difficult to separate mixture of bromides results72. At the present time, derivatives of noradamantane (see also Scheme 8), homoadamantane, and related systems are most readily obtained by more indirect methods as discussed in Section III. Bromination of ethanoadamantane (25) gives a single monobromide, however 38b). 

Treatment of l,3-dibromo-3,5-dibromomethyladamantane with zinc results in a double fragmentation of the adamantane ring 1,3,5,7-tetramethylenecyclo-octane is formed in high yield. Bromination of the product with bromine in carbon tetrachloride regenerates the starting material 3631. 

The chemistry of adamantylidene adamantane has been found to be quite unusual, due primarily to the highly hindered character of the double bond in this system. Bromination of adamantylidene adamantane gave the first isolated bromonium ion 263). Chlorination gives similar results at low temperatures while at higher temperatures chlorine is found to enter the methylene positions of the adamantyl nucleus, presumably via a protoadamantene-like intermediate 364i. 

For electrophilic and more bulky radicals, for example CnHal2n+i, selectivity increases dramatically. Whereas the selectivity for the radical chlorination (Table 1, entry 7) and bromination (Table 1, entry 8) of adamantane with Hal2 in CC14 is only approximately 5, for chlorinations with CC14 (Table 1, entries 9 and 10) and brominations with BrCCl3 (Table 1, entry 11) the selectivity increases to 21.5-27. Halogenations under metal-catalyzed GIF conditions (Table 1, entry 12) or in the presence of dioxirane (Table 1, entry 13) are less selective, because of the participation of oxygen-centered (GIF) or methyl (DMD) radicals. 

Photochlorination has been recommended for the preparation of choice of cyclodecene from cyclodecane via the intermediate chloride.Bromine is a rather weak brominating agent for alkanes and only unusually favorable substrates, like adamantane, react at a reasonable rate. The mixture HgO/Br2 is much more reactive than bromine itself, as shown by the facile bromination of 1,1,3,3-tetramethylbutane. Silver hexafluoroantimonate has also been used to activate bromine for this type of reaction. Iodine is normally ineffective in functionalizing alkanes, but use of y-irradiation of a solution of I2 in alkanes leads to unselective formation of all possible iodoalkanes. ... 

Bromination. Activation of aliphatic C-H bonds such as those exocyclic to the bridgehead atoms of adamantane via bromination with CBr (1-bromoadamantane, 70%, 1,3-dibromoadamantane, 15%) under phase-transfer conditions [50% NaOH/Cl Clj, Bn(Et)3NCl, A] is quite useful. Cyclohexane provides bromocyclohexane in 44% yield. 

A range of triflate derivatives of sila-adamantanes have been prepared from methylsilyladamantanes by cleaving the Si-Me bond with ICl/AgOTf These compounds have been used then as precursors to cationic sila-adamantanes <2002JOM(658)141>. Various C-chlorinated and C-brominated tetrasila-adamantanes have also been prepared and their chemistry explored <2000CJC1388, 1995BSF585>. 

The y-radiolysis of adamantane and related molecules has been reinvestigated using e.s.r. the predominant initial product is the 1-adamantyl radical." Contrary to previous beliefs, adamantanes react quickly (2 h) with neat liquid bromine at room... 

In the photochlorination of l,3,5,7-tetramethyl-l,3,5,7-tetrasilaadamantane both the methyl and methylene groups are chlorinated. However, selective halogenation is possible by means of photobromination [80]. The possibility to form partially brominated Si-adamantanes arises from the results presented in Table 27. Here 0.25 molar solutions of Me Ad in CCl were treated with varying amounts of bromine in mole ratios of Me AdrBr = 1 1, 1 2, 1 4 and 1 8 and irradiated with a high pressure Hg UV source. 

In a special case, BBrs is used for the bromination of hydrocarbons. Adamantane is brominated by a mixture of Bromine, BBrs, and Aluminum Bromide to give 1,3-dibromoadamantane selectively. Tetrachlorocyclopropene and hexachlorocyclopentadiene arc substituted to the corresponding bromides by BBrs and, in the latter case, addition of AlBrj and Br2 is effective to improve the result ... 

The oxidation potential of the carbon-bromine bond is close to that for the bridgehead carbon-hydrogen bond in adamantane. Thus, 2-bromoadamantane in acetonitrile undergoes mainly oxidation at the bridgehead positions, retaining the... 

Amantadine Amantadine, 1-adamantylamine (36.1.3), is synthesized from adamantane, which is first brominated with molecular bromine to make 1-bromoadamantane (36.1.1). Interacting this with acetonitrile in a Ritter reaction conditions gives 1-acetylaminoadaman-tane (36.1.2). Hydrolysis of the last with sodium hydroxide gives amantadine [1-6]. 

The hydroxylation occurs preferentially at tertiary position (adamantane C-l C-2 = 25-48 1) unless steric hindrances exist. Some configuration inversion ( 10% in cis-decaline hydroxylation at C-9) and bromination in the presence of BrCCl3 have been observed. The double bond scrambling... 

Selective monohalogenation (chlorination and bromination) can be accomplished with excess methylene halides in the presence of SbF5.535 Adamantane, for example, gives 1-chloroadamantane in 80% yield at ambient temperature in 24 h. 

Nitration of 1-phenyladamantane occurs at the para position of the phenyl ring 1981. The resulting nitrobenzene brominates on the adamantane nucleus. If, however, the nitro group is converted to an acetamide function, bromine enters the aromatic ring (Scheme 16) I98 ... 

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