Ritter-like reaction

Although fluorine is known to be a rather poor leaving group in substitution reactions, some examples have been reported for the replacement of fluorine by N-nucleophiles. Here, substitution can proceed with amines,1 -3 amides,4 amidines,5-6 hydrazines3-7 or azides.8-9 Nitriles in the presence of nitrosyl hexafluorophosphate replace fluorine in alkyl fluorides, in a Ritter-like reaction, to form tV-alkylnitrilium species, which are hydrolyzed to amides.10... 

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

Kim and co-workers prepared a series of 2,4,5-trisubstituted oxazoles 1614 in low to good yields from desoxybenzoins 1613 and nitriles (Scheme 1.411). This Ritter-like reaction works best in the presence of a 1 1 mixture of trifluoromethane-sulfonic acid-sulfuric acid. Trifluoromethanesulfonic acid or sulfuric acid alone is ineffective. Fuming sulfuric acid gave < 10% of an oxazole. The authors proposed that sulfuric acid acts as an oxidant, analogous to Tl(OTf)3 or Cu(OTf)2. ... 

In a first proof-of-principle study, we chose benzhydryl bromide 21 as a test substrate, since this compound features a relatively weak C-Br bond. If the corresponding benzhydryl carbocation is formed (see Scheme 16) and no further nucleophiles are added, the solvent (acetonitrile) will attack the cation and form a nitrilium ion intermediate. Finally, traces of water in the solvent will hydrolyze this species to from W-benzhydryl acetamide 22 in an overall Ritter-like reaction. The formation of this product from benzhydryl bromide can easily be followed by H-NMR spectroscopy. 

Alkenes react in a similar fashion giving methoxymethyl derivatives, but in this case the intermediate carbenium ion is trapped with methoxide or another nucleophile such as a nitrile to afford the methyl ether or amide in a Ritter-like reaction (eq 11). In similar fashion, silyl enol ethers give ketones (eq 12), allyl-silanes afford homologated alkenes (eq 13), and stannylalkynes are converted to propargyl ethers. ... 

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. ... 

This method was designed to produce an acetyl intermediate just like that in the failed recipe a few paragraphs above using only sulfuric acid and acetonitrile [93]. This reaction works, in theory, in a so-so manner on allylbenzene but not on safrole. This method will not make X for many reasons. So why does underground literature and DEA forensic scientists keep claiming that it does Strike doesn t know either. Let s see what the man who invented this. Dr. Ritter, had to say back in 1952 "several attempts to obtain amides from...safrol (sic) were fruitless. [94]. What makes all these people think that this will work unless no one did their homework. This is another sore spot of Strike s and... 

It is possible to synthesize cobalt complexes which are soluble in polyethylene glycols and not in. solvents like hexane, hexene, heptenal etc. Ritter et al. (1996) have reported the oxo reaction of 1-hexene in such a system. 

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

In reactions where rearrangement is likely, a rule of thumb is that the most stable available cartenium ion will lead to the product. Such thermodynamic control may be used deliberately to carry out complex rearrangements in high yields for suitable cases. When the potential cartenium ions are of similar energy, for example in Ritter reactions of unsaturated fatty acids or esters, then mixtures of products are likely. In such cases, mass spectrometry has proved to be a particularly useful analytical technique. ... 

Cristol has earned out photochemical studies on a range of cyclic halogenated substrates which yield Ritter-type products.Irradiation of the dihalides (80) in acetonitrile normally affords a mixture of the isomeric piquets (81) and (82 X = halogen), plus polar material. However, when the solvent was switched to 3% aqueous acetonitrile, significant amounts of the additional products (81 X = OH 13%) and (81 X = NHAc 16%), plus traces of (82 X = NHAc) were isolated (equation 40). These new substances are believed to result from nucleophilic attack by water or acetonitrile on a ground state carbe-nium ion-like intermediate. A number of further, closely related reactions of this type have been described.These photolyses consistently yield amide products but, unfortunately from the synthetic viewpoint, mixtures are often produced, and overall yields of the amides are not generally high. 

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