Adamantane, acetamidation

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 ... 

Alkyl cations thus formed may recombine with the nucleophile (Eq. 10) giving tri-fluoroacetates or acetamides under anodic oxidation conditions in CF3COOH or CH3CN, respectively. For example, electrooxidation of cyclohexane (7) in CH2C12/ CF3COOH yielded 84 % cyclohexyl trifluoroacetate (15) [23] oxidation of adamantane (9) gave acetamide (16) cleanly (Scheme 4) [24]. 

In the wake of the early work just described, several investigations of anodic acet-amidation of polycyclic hydrocarbons were initiated substituted adamantanes were much used in this work because of their availability and their relative ease of oxidation [1 VO-174]. The results are generally explicable in terms of expected stabilities of intermediate carbocations and competition between proton loss and C-C bond cleavage. Difunctionalization of adamantanes is also possible using anodic acetamidation [Eq. (50)] [174]. 

The physical technique with the greatest potential for synthetic applications of Ritter-type reactions is electrochemistry. A selection only of examples is discussed here. Synthetic chemists unfamiliar with this technique will find the review by Eberson and Nyberg an informative and entertaining introduction to this area. Electrochemical Ritter reactions may be performed through anodic substitution of a hydrogen by the nitrile, followed by hydrolysis of the nitrilium ion intermediate, as shown in Scheme 42. The majority of reactions investigated have been anodic acetamidations using hydrocarbons, alkyl halides, esters or ketones as the substrate. In some cases, such as reaction of the adamantane derivatives (83), the yields of amide product are excellent (Scheme 43). 

In general, treatment of carbonium ions with nitriles under a variety of conditions yields A -substituted amines. Anodic oxidation in acetonitrile converts selected aliphatic compounds to acetamides, e.g. adamantane to adamantylacetamide (equation 22). ... 

The anodic conversion of tertiary C—H functions (without any specific activation) is possible, yet it needs rather high potentials. One typical example is certainly that of adamantane [42], the oxidation of which can be achieved in acetonitrile. Under these conditions, the corresponding acetamide (via Ritter reaction) was obtained. 

It is prepared by brominating adamantane and treating the resulting bromo derivative with acetonitrile in the presence of sulphuric acid to obtain N-(l-adamantanyl) acetamide. This on alkaline hydrolysis and treatment with hydrochloric acid affords the official compoimd. 

When the nitration of adamantane with NOJBF4 is carried out in acetonitrile upon aqueous workup JV-(l-adamantyI)acetamide is obtained in 88% yield. Similarly, norbomane yields N-(exo-2-norbonyl)acetamide in 77% yield. Bicyclo[2.2.2]octane gives in 73% yield the corresponding amides. 

N-Adamantyl acetamide or N-diamantyl acetamide can be synthesized by direct one pot amidation of adamantane or diamantane with acetonitrile in the presence of [Mo(CO)g] and bromotrichloromethane in aqueous medium (Scheme 10.9) [58]. Reaction occurs in close vessel at 140-150°C... 

The oxidation of substituted adaman-tanes has been studied in detail by Miller [21, 22] and Mellor [23-25]. Cpe in a divided cell produces two types of products by substitution at the tertiary carbon atom substitution of hydrogen for acetamide with retention of the substituent X in the adamantane molecule [substituent X (yield in %) H (90), Cl (91), F (65), CH3 (91), CO2CH3 (64), CN (41)1 and substitution of X for acetamide [Br (89), CH2OH (37),C0CH3 (44), oh (41),0CH3 (58)1 [22]. Cleavages of 1-acetyl-, 1-bromo... 

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