Acetic acid Ritter reaction

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-... 

The conversion of 2,5-pyridinedicarboxylic acid Af oxide (284) inaceto-nitrile/acetic anhydride to the corresponding 6-amino-nicotinic acid (288) seems to be a Ritter reaction of intermediate cation 285 with acetonitrile, followed by rearrangement of intermediate 286 to 287, which is then saponified by potassium hydroxide to give 49% of 6-aminonicotinic acid (2M) and 8% of 6-hydroxynicotinic acid (289) (83EUP90I73). 

Hydration can also be accomplished by the Ritter reaction (treatment with t-butanol in sulfuric acid-acetic 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. 

The outcome of the Ritter reaction can also be determined by kinetic control. For example, conflicting reports have appeared in the literature regarding the behavior of alcohol (9), the alternative products (10) or (11) both having been reported. These differences result from the order of addition of the reagents. The amides (10) result if the alcohol is mixed first with the nitrile and acetic acid, the sulfuric acid being added last. In this instance (kinetic control), the initial cations are reacted to (10) as they are produced. Conversely, if (9) is mixed first with the acids, and then the nitrile is added, the products (11) result. In this case (thermodynamic control) cartenium ion rearrangement precedes Ritter reaction (Scheme 5). For less clear-cut cases, the use of less acidic conditions and/or lower temperature results in greater isomer selectivity, but at the cost of lower overall yields. ... 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

The reaction of nitriles with aromatic aldehydes is carried out at heating the reactants to 50-70°C with a 1 -h 10 (v/v) mixture of concentrated sulfuric acid and glacial acetic acid. The cycloaddition reaction is regiospecific. The oxazines 21 (equation 10) are formed as diastereoisomeric pairs which are free from their regioisomeric products in the limit of the NMR analysis. Precursors used were benzonitrile and acetonitrile as well as acetaldehyde, benzaldehyde and its substituted derivatives, and a number of the olefins having various structures. Until now, the reaction of aldehydes with nitriles was interpreted as an extension of the Ritter reaction. The initial O-protonation of aldehyde 22 is postulated to form in the presence of acid the hydroxycarbenium ion 23 which then reacts as a cationoid electrophile with the nitrile (equation 11) giving the nitrilium ion 24. 

Carbenium ions can be produced from numerous different functionalities via many different techniques, and consequently the Ritter reaction represents an extremely versatile technique for the formation of amides. For example, we have above illustrated the formation of a stable carbenium ion from alcohols and alkenes, and Reddy has reported the use of an ester as a source of the necessary carbenium ion.5 In this case, t-butyl acetate (12) was converted to the corresponding cation with catalytic concentrated sulphuric acid and was reacted with a wide variety of aromatic nitriles 11 with commendable success. 

CAN-mediated nitration provides a convenient route for the introduction of a nitro group into a variety of substrates. Alkenes on treatment with an excess of sodium nitrite and CAN in chloroform under sonication afford nitroalkenes. When acetonitrile is used as the solvent, nitroacetamidation occurs in a Ritter-type fashion. However, the attempted nitroacetamidation of cyclo-pentene-1 -carboxaldehyde under similar conditions resulted in the formation of an unexpected dinitro-oxime compound. A one-pot synthesis of 3-acetyl- or 3-benzoylisoxazole derivatives by reaction of alkenes (or alkynes) with CAN in acetone or acetophenone has been reported. The proposed mechanism involves a-nitration of the solvent acetone, oxidation to generate the nitrile oxide, and subsequent 1,3-dipolar cycloaddition with alkenes or alkynes. The nitration of aromatic compounds such as carbozole, naphthalene, and coumarins by CAN has also been investigated. As an example, coumarin on treatment with 1 equiv of CAN in acetic acid gives 6-nitrocoumarin in 92% yield. ... 

A Ritter reaction can be carried out on atactic polyacrylonitrile with A hydroxymethylamides of acetic, benzoic, and benzene-sulfonic acidsWhen the same reactions are carried out with W-hydroxymethylimides of succinic or phthalic acids in tetramethylene sulfone, there is a stronger tendency toward crosslinking. 

A variation on the Ritter reaction, suitable for the transformation of primary secondary, and tertiary alcohols to acetamides, involves thionyl chloride in acetonitrile. Reduction of the crude products (Scheme 17) with zinc-acetic acid converts any chloroacetamide product into the acetamide, and overall yields are moderate to good. 

---