Lewis acids Ritter reaction

Only alcohols that give rise to fairly stable carbocations react (secondary, tertiary, benzylic, etc.) non-benzylic primary alcohols do not give the reaction. The carbo-cation need not be generated from an alcohol, but may come from protonation of an alkene or from other sources. In any case, the reaction is called the Ritter reac-Lewis acids, such as Mg(HS04)2, have been used to promote the reac-... 

Br prevents side reactions and makes BiBr3 a better Lewis acid catalyst, which is in accordance with our work BiBr3 affords only Ritter reaction products in the high dielectric constant solvent CH3CN, while BiCl3 originates a mixture of both v7 -/V-acylamino-hydroxy compounds and chlorohydrins. 

The acid used in the Ritter reaction is usually sulfuric acid, although other acids such as perchloric, phosphoric, polyphosphoric, formic and sulfonic acids have been used. Lewis acids such as aluminum trichloride and boron trifluoride are also occasionally used. However, high yields are generally best obtained with sulfuric acid. The choice of solvents varies among sulfuric acid, glacial acetic acid, acetic an-... 

Reaction of sugar lactone with ester enolate (the Claisen condensation) gives -keto ester, the resulting 1,3-dicarbonyl compound immediately reacts with the hydroxyl group present in the same molecule to afford a lactol with an axial hydroxyl group. In a recent example shown in O Scheme 4 [8], the product of the reaction was further transformed to the corresponding nitrile or amide by addition of cyanide or a Ritter reaction with benzonitrile in the presence of TMSOTf as a Lewis acid. 

Lewis acids such as tin(IV) chloride, boron trifluoride-acetic acid and boron trifluoride-etherate, are also effective in promoting the Ritter reaction. In general, the original technique is more efficient, but use of Lewis acids can sometimes signiflcantly influence the proportions of products in a mixture and has advantages when relatively sensitive substrates are present. 

Earlier mention has been made of the use of Lewis acid and Friedel-Crafts reagents as initiators of carbenium ion formation. Another versatile device is to employ a metal to assist in generation of the carbenium ion. In its simplest form, addition of silver(I) ion to an alkyl halide is an excellent technique for encouraging reaction by means of the 5n 1 pathway. This process was first applied to the Ritter reaction by Cast and Stevens, but yields obtained were modest. A recent elegant application of this technique is the two-step conversion of dodecahedrane into its acetamide derivative (Scheme 45). ... 

It was also found recently that direct selective substitution of aliphatic hydrocarbons via a supposedly electrophilic mechanism can be achieved by use of F-TEDA-BF4 [202]. Depending on the exact reaction conditions, either alkyl fluorides or Ritter-type products are obtained (Scheme 2.91). Relatively short reaction times favor the formation of the fluorides, longer heating with F-TEDA-BF4 in acetonitrile favors the formation of acetamides, especially in the presence of additional BF3 OEt2 as Lewis acid catalyst [203]. 

The yields of the pyrimidines 147 and the pyridines 151 are not high and vary greatly, depending on the structure of the starting materials. The latter can also determine the nature of the product. Thus, a mixture of 2,4-dimethyl-6-phenylpyrimidine, 2,4-dimethyl-4,6-diphenyl-4//-l,3-oxazine and 1-chloro-l-phenylethene was obtained by refluxing a 1 3 3 ratio of the acetophenone-benzonitrile-phosphorus oxychloride mixture, followed by treatment of the crude product with sodium carbonate solution .It has been shown that addition of an additional ketone molecule to the iminium intermediate is an alternative to the formation of the A -acylenamines and this route is catalyzed by aluminum chloride. Auricchio and coworkers believe also that the reaction of ketones with nitriles catalyzed with both protic and Lewis acids must be considered as a Ritter reaction (see, however, Section V.C). The cationic intermediate 152 thus formed can undergo either a proton shift giving enamide 153 or addition of another ketone molecule... 

In general, these alcohol-based dehydrative A-alkylation reactions can be classified into two categories. One is the direct nucleophilic substitution of the hydroxy group by amines/amides mediated/catalyzed by Bronsted acids, Lewis acids, or TM complexes via formation of carbocation or coordinated cationic metal complexes under acidic conditions (Scheme 2) [16-20]. The famous Ritter reaction of nitriles and alcohols giving alkylated amides may be classified as one of these reactions, in which the nitriles serve as the A-nuleophile (Eq. 2) [21, 22]. 

Boiling compound 29 in liquid bromine for 4h also leads to formation of compound 49, but in higher yield. They were not able to add a bromine atom to the adamantane ring even when using catalysts (Lewis acids) conventionally used for difficult bromination reactions. Regardless of the reaction conditions, they could detect formation of only compound 49. They converted compound 49 to the acetoamino derivative via the Ritter reaction [45]. 

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