Ritter-type reactions

Regio- (Markovnikov) and stereo-specific (anti) incorporation of MeCN (a Ritter-type reaction) has been observed upon bromination of a series of olefins, carried out in this solvent187. The degree of this incorporation depends on the olefin structure and on the initial reagent concentrations and ratios. Thus, when performed at low initial concentrations and with the initial B /alkene ratio >2, this reaction can be used preparatively187. 

Eq. (5.344)]. The suggested mechanistic pathway is a Ritter-type reaction with the involvement of the bicyclobutonium ion 288. 

When o-aminocarbonitriles 48 (R2 = R3 = Me) or 52 were reacted with jY-arylcyanamides in the presence of dry hydrogen chloride gas followed by aqueous workup, a mixture of 2-amino-3-aryl-4-iminothieno[2,3-d]-pyrimidines 65d and the corresponding thieno[2,3-d]pyrimidin-4(3//)-ones 66b was isolated. The formation of the latter as a minor product for each derivative was rationalized to proceed via the guanidine intermediate 67, which hydrolyzed through a Ritter-type reaction and then cyclized during workup (93JHC435). 

The participation of nitrilium salts has also been postulated42 in the Schmidt reaction and in some Beckmann rearrangements when concentrated sulfuric acid is employed. Hill43 has demonstrated recently that some Beckmann rearrangements carried out in a concentrated sulfuric acid medium are Ritter-type reactions in which the nitrile formed in situ from the oxime combines with a carbonium ion to yield a nitrilium salt, which, when diluted with water, leads to the N-alkylamide. 

The use of haloalkenes or halohydrins in Ritter-type reactions has resulted in the development of an oxazoline (105) synthesis85 yields are 60-70%. The formation of 2-ethyl-4,4-dimethyl-5,6-dihydro-4Zf-1.3-oxazine (106)55 from 1-chloro-3-methyl-2-butene and propio-nitrile in the presence of sulfuric acid has a similar basis. 

The reaction starts with loss of two electrons from the aromatic system of 39a this is stabilized by loss of a 2-butyl carbonium ion, which reacts with acetonitrile in a Ritter-type reaction, and by attack by the nucleophile pyridine. The second loss of two electrons maj occur before or after the ring closure. Similar internal substitution reactions are of potential value for the synthesis of heterocyclic compounds. 

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. 

The acidic salts of heteropolyacids, in which the protons are partially substituted with Cs+, are active for acid-catalyzed reactions such as Friedel Crafts reactions, Ritter-type reactions, and skeletal isomerization of alkanes. The... 

Bimolecular trapping of phenoxonium ions by nucleophilic yr-bonds can lead to cyclized products when attack occurs at the or /io-position. For instance, a Ritter-type reaction occurs when MeCN is used as solvent in the absence of other nucleophiles, leading to a useful synthesis of benzoxazoles (XLV) [48] ... 

The reactive intermediate is considered to be RS", which adds to the carbon-oarbon double bond, probably forming an intermediate episulfonium ion as in Eq. (18). This by a Ritter-type reaction followed by hydrolysis leads to the final products, as in Eqs. (19) and (20). 

A Ritter-type reaction is also observed during the anodic oxidation of phenylthio-methane derivatives [186] of the type shown in Eq. (55), which summarizes the proposed reaction mechanism. 

In principle, any functionality capable of producing a carbenium ion under strongly acidic conditions will be able to participate in a Ritter-type reaction. Such classes of compounds include alcohols, aldehydes, alkanes, alkenes, alkyl halides, carboxylic acids, dienes, epoxides, esters, ethers, glycols, ketones, IV-methylolamides and oximes. Consequently, an enormous number of examples is reported and only a representative selection can be presented here. A comprehensive listing of examples reported up to 1966 is provided in the review by Krimen and Cota. ... 

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. ... 

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). 

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