Friedel from amides

Another drawback to the use of amino-substituted benzenes in electrophilic aromatic substitution reactions is that Friedel-Crafts reactions are not successful (Section 16.3). The amino group forms an acid-base complex with the AICI3 catalyst, which prevents further reaction from occurring. Both drawbacks can be overcome, however, b3 carrying out electrophilic aromatic substitution reactions on the corresponding amide rather than on the free amine. 

The mono-silylated or free acetamides, which are liberated during silylation with 22 a, can, furthermore, interfere with any subsequent reaction, e.g. with electrophiles. Thus in the one-pot/one-step silylation, Friedel-Crafts catalyzed, nucleoside synthesis starting from protected sugar derivatives and pyrimidine or purine bases, the mono- or bis-silylated amides such as 22 a can compete with less reactive silylated heterocycHc bases for the intermediate electrophilic sugar cation to form protected 1-acetylamino sugars in up to 49% yield [42, 47]. On silylation with trimethylsilylated urea 23 a the Hberated free urea is nearly insoluble in most solvents, for example CH2CI2, and thus rapidly precipitated [43]. 

A series of calpain I inhibitors such as 184 were prepared in a similar fashion from a-chloronitrile 185 in four steps (Scheme 24) <2001JME3488>. The key steps of this synthesis are the aforementioned Friedel-Crafts-type reaction of chloronittile 185 with CISO3H and a one-pot amidation/N-alkylation of dichloride 186 which furnishes the benzosulfonamide core 188 of these inhibitors via intermediate 187. 

Furyl ketones can be easily obtained by Friedel-Crafts acylation of furans. They can also be obtained from derivatives of furan-2-carboxylic acid such as the amides, nitriles and chlorides by literature reactions. The 3-furyl ketones are also obtained by similar methods. 

V. Remote aromatic metalation. An anionic Friedel-Crafts equivalent for the regioselective synthesis of condensed fluorenones from biaryl and m-teraryl 2-amides. /. Org. Chem. 1991, 56,1683-1685. 

The ketone comes from a Friedel-Crafts reaction, the cyanohydrin was hydrolysed in two stages via the amide 23 and an excess of MeMgl on the ethyl ester 20 R = Et gave the diol6 19. 

Planar chiral phosphaferrocene-oxazolines (379) constitute another family of complexes that are usefiil as ligands in asymmetric catalysis. Preparation of these takes advantage of a modified Friedel-Crafts acylation of (373) and an unusual conversion of the resulting trifluoromethyl ketone into an amide that is then cyclized to an oxazoline. The diastereomeric complexes thus formed are chromatographically separable and are used in a palladium-catalyzed asymmetric allylic substitution. Modification of this complex by using the anion derived from 3,4-dimethyl-2-phenylphosphole gives more... 

A Acetophenone derivatives can be prepared from benzene by a Friedel-Crafts acylation. The derived oxime, formed using hydrox-ylamine, undergoes a Beckmann rearrangement to produce the amide hydrolysis yields the amine (Scheme 8.4). 

Analysis by the amide method (see Chapter 8) leads back to amine (6) which can be made from ketone (7), a simple Friedel-Crafts product. 

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