Ritter-type processes

Ritter-Type Process for ds-l-Amino-2-Indanol Synthesis.465... 

Ritter-Type Process for c/s-1-Amino-2-Indanol Synthesis... 

The Ritter reaction as originally reported involved generation of a carbenium ion intermediate under strongly acidic conditions, followed by reaction with the nitrile component. Not surprisingly, other means of generating the carbenium ion, or related chemical species, also result in Ritter-type processes. These newer developments have greatly added to the overall synthetic versatility of the reaction over recent years. 

West and Koch also reported an example of solvent capture of zwitterions derived from 4-pyrones 25a and 25b by acetonitrile in the presence of Hthium perchlorate (Scheme 7) A Ritter-type process was invoked to explain the isolation of bicycHc oxazolines 26, together with 2-pyrones 27. It is important to... 

Since the solvolysis of intermediates occurred so easily in moist acetone, the stoichiometric reaction of la was repeated in methanol as solvent, resulting in the methyl ether 5a being isolated. More importantly, when the reaction was performed in dry acetonitrile, the corresponding acetamide (6a) was produced indicating that a Ritter-type reaction had occurred. Hence, C-N as well as C-0 bonds can be formed by this process. In a further development of this reaction, the intermediate nitrilium salts have been intercepted by azide ion, giving good yields of tetrazoles. 

Due to the important role of nitrogen functional groups, the addition reactions of an electrophilic selenium reagent and a nitrogen nucleophile to a carbon-carbon double bond represent a synthetically relevant process with potential practical applications. Among the reactions of this type which have been described already, perhaps the most important contribution is represented by the Ritter-type amide synthesis described by Toshimitsu and Uemura [48a, 48b]. The addition of a phenylselenyl and of an acylamino group to a mono or a 1,2-disubstituted olefin was accomplished by treating the olefin with PhSeCl in acetonitrile and water in the presence of trifluoromethanesulfonic acid. 

The isolation of oxazole derivatives from Ritter-type reactions dates back to 1893, when Japp and Murray reported that benzoin and sulfuric acid reacted with nitriles (equation 33). Better yields of such products are obtained from reaction of chloro ketones (54) with nitrile-SnCU complexes (equation 34). Likely mechanisms for these processes have been discussed by Meyers and Sircar. ... 

As an extension of the amidoseleniation processes discussed previously, imidates (the third Ritter intermediate) may be utilized as precursors for the synthesis of cyclic amides (Scheme 67) and lactams (equation 52). Such combination of imidate and onium ion processes has much potential for further extension of Ritter-type chemistry. 

In a report describing acid-promoted Ritter reactions involving a-methylene-)5-hydroxyesters, an I -type process was found to be the preferred mechanism. For compound (104), both Ritter reaction products (105 and 106) are obtained. In order to rule out 5 2 or Sf 2 mechanisms, kinetic analysis was performed, kinetic isotope effects were evaluated, and both Hammett and Eyring plots were done. The mechanistic studies were consistent with an I -type process being preferred with initial formation of the oxonium cation, loss of water, and formation of the allylic acarbocation (107). DFT calculations indicated nucleophilic attack at the terminal carbon (107b, 5 10 was favored by about 2.6kcalmol over attack at the benzylic position (107a, 5 1) (Scheme 23). 

The reaction differs from the Ritter reaction by the two types of electrophilic activation of the reagents and by the two types of rearrangement of nitrilium 285 and carboxonium ions 288 (equation 94). Besides, this interaction proceeds at an oxidation level of two, while the Ritter reaction occurs at an oxidation level of one17. While it may be shown that A-acyliminium ions 365 can be obtained from a carbonyl compound and a nitrile via the Ritter reaction, then it is only the second step b) in a three-step process where the first step (a) is the reduction of carbonyl compound 364 to alcohol 366 and the third step (c) is an oxidative dehydrogenation of amide 369 obtained3 (equation 105). 

Caprolactam can also be polymerized under anhydrous conditions using strong bases as catalysts. This was already reported by Schlack in 1938 [l7j. r.m. Joyce and D.M. Ritter [32] at DuPont discovered in 1939 that this anionic polymerization proceeded with a much higher rate than the hydrolytic process and that it could be carried out below the melting point of the polymer to yield products of low residual monomer content, so that they needed no extraction. In spite of these obvious advantages this type of polymerization at first did not enter into commercial practice because of poor reproducability, unstable melt viscosity and poor product color [29]. 

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