Benzene adamantylation

Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%)." In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

Figure 19. Left) l,3-Dichloro-5-(l-adamantyl)benzene monomer and (Right) adamantyl-substituted poly(m-phenylene), which is shown to have a high degree of polymerization and stability, decomposing at high temperatures of around 350 °C. Taken from Ref [89] with permission.

FeCl3-doped K10 montmorillonite was used to promote adamantylation of benzene to form 1-phenyl and 1,3-diphenyladamantanes in ratios depending on the amount of catalyst 193... 

The solid acid catalyzed adamantylation of substituted benzene derivatives was studied with the aim to achieve high para regioselectivities. Of various acidic resins, zeolite HY, sulfated zirconia, perfluorolkanesulfonic acids, and phosphotungstic acid, Amberlyst XN-1010 was found to be the catalyst of choice to afford para-substituted alkylbenzenes with selectivities exceeding 70%.398 In further systematic studies with a Nafion-H-silica nanocomposite catalyst,399 and various... 

Bredt s rule. In this way, 1-adamantyl p-methoxyacetophenone 86a was forced to yield only cyclobutanols 87a and 88a as photoproducts [281]. Whereas (benzene) solution phase irradiations of 86a yielded a 2.6 ratio of 87a/88a, the solid state photoproduct ratio, 0.5, favors the more sterically hindered cyclobutanol. X-Ray diffraction studies predict a chair-like y-hydrogen abstraction pathway for 86a (in contrast to the boat-like transition states of 82) in which the C=0-Ha distance is 2.67 A. Other abstractable hydrogens (Hb) are at least 0.3 A farther from the carbonyl oxygen (Scheme 44). If i-BR has a conformation which mimics that of the ketone, its least motion pathway favors formation of the more sterically hindered cyclobutanol 88a. 

The synthesis of a number of substituted thioureides by treatment of isothiocyanates 2 and 30-32 with aniline, 2-aminopyridine, 1-adamantyl-amine, benzylamine, 2-aminobenzimidazole, 2-aminobenzothiazole, o-bromoaniline, 2-aminopyridine, 5-amino-1 -phenylpyrazole-4-carboxylic acid, and various classes of sulfamines, in benzene or xylene solution, has been reported.54... 

Boron tris(triflate) has also been tested in the adamantylation of benzene and toluene with 1-haloadamantanes [Eq. (5.87)] and2-haloadamantanes.232B(OTf)3 is a highly active catalyst to promote the transformation in very short time under mild conditions to yield isomeric aryladamantanes and adamantane byproduct (Table 5.15). Of the isomeric 1-tolyladamantanes, 1-meto-tolyladamantane predominates, whereas the para isomer is the main product of the 2-tolyladamantanes. The ortho isomers were... 

Table 5.16. Adamantylation of Benzene-Toluene Mixture with 1-Haloadamantanes in the Presence of B(OTf)3 ... 

Laali et al.234 have developed a method to the highly selective pura-adamantylation of arenes (toluene, ethylbenzene, anisole) with haloadamantanes (1-chloro- and 1-bromoadamantane, l-bromo-3,5,7-trimethyladamantane) and 1-adamantanol promoted by triflic acid in butylmethylimidazolium triflate [BMIM][OTf] ionic liquid. In contrast to reactions mn in 1,2-dichloroethane, little or no adamantane byproduct was detected in [BMIM][OTf. Furthermore, no isomerization of para-tolyladamantane was observed supporting the intramolecular nature of the formation of meta isomers. In competitive experiments with benzene-toluene mixture (1 1 molar ratio), high substrate selectivities were found (kT/kB = 16-17) irrespective of the alkylating agent. This is in sharp contrast to values about unity measured in 1,2-dichloroethane. 

Irradiation with a mercury lamp of (diacyloxyiodo)benzene (64) in the presence of disulfide, generates the corresponding alkyl sulfide (65) together with iodobenzene and carbon dioxide (eq. 2.31) [75, 76]. This is useful for the preparation of adamantyl sulfides or selenides, since the preparation of such caged tert-alkyl sulfides or selenide is not so easy with polar reaction methods. 

To a mixture of adamantyl bromide (0.5 mmol) and trifluoroacetate salt of lepidine (2.5 mmol) in benzene (6 ml) were added (trimethylsilyl)silane (1.0 mmol) and AIBN (1.0 mmol). The mixture was heated at 80 °C for 14 h under an argon atmosphere. After the reaction, the reaction mixture was washed with sat. aq. NaHC03. The organic layer was dried over Na2S04. After removal of the solvent, the residue was chromatographed on silica gel to give 2-(l-adamantyl)-4-methylquinoline in 90% (125 mg) yield [33]. 

Some bridgehead amines such as 4-iodo-l-cubylamine (58%) and 1-adamantyl-amine (85%) were also obtained in this way [47]. The direct formation of alkylammonium tosylates is advantageous because of the instability of some amines of this type. No special precautions, as with BTI, were needed with HTI which, however, did not work with some cyclic carboxamides also, malonamide did not undergo degradation but tosyloxylation, affording a-tosyloxymalonamide (81%) [48]. The reaction involved the intermediacy of TV-phenyliodonium salts (RCONHI + Ph TsO-), which were actually isolated from carboxamides and [methoxy(tosyloxy)iodo]benzene [49]. 

When radical pairs are produced by a cleavage of ketones, and the loss of CO is prevented on energetic grounds, fragments of the reactions of the primary radical pair become important. Deoxybenzoins (15)30) or adamantyl ketones (20)25,30) provide examples of such systems. The photodecomposition of l,2-diphenyl-2-methyl-pro-panone (15)30) illustrates an example of a photofragmentation in reaction (Scheme VIII). The ratio of the major products are highly dependent on solvent environment. For example, the photochemistry of this compound in acetonitrile or benzene yields... 

The effect of the micelle environment on the photolysis of adamantyl ketones is dramatic31). The major products in the photolysis of phenyladamantyl ketone (20) in benzene are shown in Scheme IX. However, in HDTC1 only (22) is formed in significant amounts. Minor products are (16) (7%) and two new products AdOH (25) (3 %) and benzil (18) (3 %). The appearance of large amounts of adamantane... 

Further support of this mechanism has been advanced by a kinetic study of the decomposition of 1-adamantyl chloroformate . The activation parameters, however, for the decomposition of this chloroformate in benzene (A/f = 21.61 0.17 kcal.mole , AS = —12.03 + 0.59 eu) do not differ significantly from those for a-phenethyl chloroformate in toluene (Table 11). 

One of the first applications of fluorous synthesis was the use of a fluorous tin hydride 1 (Scheme 13) in radical reactions. The fluorous chains on the tin enable removal by fluorous-organic extraction, but at the same time, the solubility of 1 in benzene and other organic solvents is dramatically decreased. Consequently, reduction of 2 using 1 in benzene gave only low yields of reduced product. However, BTF is able to solubilize both the organic substrate and the fluorous reagent 1, and reduction of adamantyl bromide in BTF gave adamantane 3 in 90% yield (Scheme 13). 

The synthetically most important reaction that belongs to this category would be [4+2] cycloadditions of highly congested thiophene dioxides with alkynic dienophiles (Scheme 55) [39,40,159]. These reactions afford o-di-ferf-butyl-, o-dineopentyl-, and o-di(l-adamantyl)benzene derivatives in good yields, synthesis of which is very difficult by other means. 

Other ceramide analogs, 5R-OH-3E-Cg-ceramide, adamantyl-ceramide and benzene-C4-ceramide selectively inhibited the growth of drug-resistant human breast cancer cell lines (SKBr3 and MCF-7/Adr) (Crawford et al.,... 

Fort and Lindstrom have demonstrated that there is no significant difference in the magnitude of the benzene-induced shifts of t-butyl and adamantyl halides. They have suggested on this evidence that in... 

Alkyldenitration by the 1-adamantyl radical in / ara-substituted nitrobenzenes (/7-X-C6H4-NO2) is an efficient process only for electron-poor arenes. Thus, while for anisole (X = OMe), benzene (X = H) and toluene (X = Me) derivatives no ipso products were observed, the analogous reaction with nitrobenzenes bearing electron withdrawing substituents (X = NO2, CN, SO2R, CO2R, COMe, CHO) afforded the corresponding alkyldenitration products in 45-60 /) yield [30]. The effect of the... 

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