Nitrilium chloride

The hydrolysis in acetone-water of the azomethine derivatives 184 to the corresponding amides has been investigated by Ugi et al., (1962). An SN1 mechanism, probably involving nitrilium chloride ion-pairs, has... 

The mechanism is not fully understood, but it is very similar to the mechanism of the Gattermann-Koch formylation. The first step is the formation of a nitrilium chloride that is subsequently transformed to an imino chloride from which the reactive species, the iminium ion is generated. 

Detailed mechanistic studies by Fodor demonstrated the intermediacy of both imidoyl chlorides (6) and nitrilium salts (7) in Bischler-Napieralski reactions promoted by a variety of reagents such as PCI5, POCI3, and SOCh)/ For example, amide 1 reacts with POCI3 to afford imidoyl chloride 6. Upon heating, intermediate 6 is converted to nitrilium salt 7, which undergoes intramolecular electrophilic aromatic substitution to afford the dihydroisoquinoline 2. Fodor s studies showed that the imidoyl chloride and nitrilium salt intermediates could be generated under mild conditions and characterized spectroscopically. Fodor also found that the cyclization of the imidoyl chlorides is accelerated by the addition of Lewis acids (SnCU, ZnCh), which provides further evidence to support the intermediacy of nitrilium salts. ... 

Side reactions consistent with decomposition of intermediate nitrilium salt 7 have also been observed, including retro-Ritter reactions that afford alkenes (8), and VonBraun reactions that provide alkyl chlorides (9). ... 

A more practical solution to this problem was reported by Larson, in which the amide substrate 20 was treated with oxalyl chloride to afford a 2-chlorooxazolidine-4,5-dione 23. Reaction of this substrate with FeCL affords a reactive A-acyl iminium ion intermediate 24, which undergoes an intramolecular electrophilic aromatic substitution reaction to provide 25. Deprotection of 25 with acidic methanol affords the desired dihydroisoquinoline products 22. This strategy avoids the problematic nitrilium ion intermediate, and provides generally good yields of 3-aryl dihydroisoquinolines. 

Diphenyl-1//-1,2,4-benzotriazepines 3 are formed in good yield by the cydization of the nitrilium salts 2, which in turn are prepared from the benzenehydrazonyl chloride 1 and nitriles... 

Lastly, Livinghouse s approach to the tricyclic core of 4 is highlighted by an acylnitrilium spirocyclization [19d], Exposure of isonitrile 48 to thiophenyl acetyl chloride provides an intermediate chloramine (49) that, in the presence of a silver salt, eliminates the chloride to form a nitrilium ion (R-N = C+-R). The nitrilium is attacked by the nucleophilic aromatic ring to furnish spirocyclic imine 50 in high... 

A mild and greener approach to the synthesis of 1,2,4-triazoles by the dipolar cycloaddition of nitrilimines with nitriles has been reported. The nitrilium intermediates were generated in situ from hydrazonyl chlorides 120 and reacted with the nitriles in a one-pot process. Yields of the 1,3,5-trisubstituted products 121a-o were good in the majority of cases (Equation 37 and Table 20) <2005H(65)1183>. 

Perhaps the earliest examples of a polar cycloaddition are some involving nitrilium salts. Meerwein et al. found that A -arylacylimido chlorides (70) in the presence of Lewis acids (usually added in the form... 

The same general method was used by Schmidt (see 74) to generate nitrilium ions for addition to phenylacetylene. Normal addition of the nitrilium ion (76) occurred, affording the hydrobromide (77) of 2,4-diphenylquinoline, presumably via the carbonium ion (78). Interestingly, the analogous N-arylacylimido chloride in which the R group was... 

Treatment of N-oxides with imidoyl chlorides or nitrilium salts can lead to intramolecular amination. This is a useful direct method for the introduction of a 2-arylamino group into the pyridine ring (Scheme 99) (74JOC1795). The by-products that are isolated in some of these reactions are believed to be formed as shown. When the a-positions are blocked a... 

Carbonsaure-nitrile konnen mit starken Alkylierungsmitteln [z. B. Trifluor-methansulfonsaure-methylester222,223, Eisen(IIl)-chlorid/2-Chlor-propan224] zu den entsprechenden Nitrilium-Sal-zen umgesetzt werden. Aus N-Methyl-acetnitrilium-trifluormethansulfonat und Diamino-ma-leinsaure-dinitril erhalt man je nach Reaktionsbedingungen 5-Amino-4-aminocarbonyl-l,2-dimethyl-, 5-Amino-4-cyan-l,2-dimethyl- oder 5-Amino-4-(cyan-imino-methyl)-l,2-dimethyl-imid-azol222 223. 

IH- 1,2,4-Benzotriazepines can be prepared in good yield by the reaction of some hydrazidoyl chlorides of type (461) with cyano compounds. The reaction is thought to proceed via the nitrilium salt (462). The products (463) are stable to alkali but are hydrolyzed in acid to give 1-phenyl-3R-indazoles (74T195). 

H-1,2,4-Benzotriazepines (506) can be prepared by reaction of hydrazidoyl chlorides (504) with cyano compounds via the nitrilium salt (505) (74T195). 

The kinetics and mechanism of the dechlorination of /V-aryl 2-oxo-2-phenylamino-ethanehydrazonyl chlorides (89) in triethylamine in aqueous dioxane at 25 °C giving the oxanilic hydrazide (91) and 1,4-diaryl-1,2,4,5-tetrazine (92) have been examined.80 The slow step of this interesting reaction is considered to be the breakup of the nitrilium imide (90). 

The oxanihc hydrazide and tetrazine fonned when /V-aryl-2-oxo-2-phenylamino-ethanehydrazonyl chloride (120) is treated with Et3 N in 1,4-dioxane-water (4 1, v/v) at 25 °C aiise from tlie intermediate nitrilium amide (121).101 A kinetic study has now established that (121) is fonned from (120) according to Scheme 15. The second-order rate constant kohs = 037<7X — 0.77, where pobs = 0.37 = pa + Pu since pa 1.18 [cf. that determined for acid dissociation of PhNHCON(CN)=NNHCgH4X], it has been possible to evaluate pl = —0.81, which compares favourably with the value p = —0.63 for C—Br heterolysis of PhC(Br)=NNHCgH4X in the same solvent. 

The marked stereospecificity observed in the addition of nucleophiles to nitrilium ions should also be apparent in the reverse process, i,e., in the loss of an atom or group leading to the nitrilium ion formation. Johnson and co-workers (19, 20) have prepared several pairs of isomeric 0-alkylhy-droxamoyl chlorides 51 and 52. These compounds undergo unimolecular loss... 

Scheme 13). A possible mechanistic pathway involves imidoyl chloride and nitrilium cation intermediates. A similar reaction of A.A/ -diacetyl-1,2-diaminobenzene and phosphoryl chloride with the 2,2 -diindolyl-methane 12 did form the macrocycle 46, but only in a very low yield12 (Scheme 13). 

We should also mention that Ziegler et al.72 have described the formation of l,3-oxazine-4-ones (91) by reactions taking place between benzylmalonyl chloride and several nitriles. They interpret the process as taking place via an IV-acyl-nitrilium salt (90). 

C—C—O+N—C. a-Hydroxy ketones react with monosubstituted cyanamides under the influence of sodium hydroxide to yield derivatives of 2-aminooxazole (equation 125) (76S591). Oxazoles are obtained by the action of nitriles on a-diazo carbonyl compounds in the presence of Lewis acids, such as aluminum chloride or boron trifluoride, and the reaction is thought to involve the intermediacy of nitrilium salts (equation 126). Nitrilium salts are also the effective agents in the formation of oxazoles from a-chloro ketones and nitriles in the presence of tin(IV) chloride (equation 127). 

It is assumed86 that this reaction proceeds via the cationoid intermediates 251 and 252 which are analogous to those described by Zielinski95,96 (equations 48 and 50). The same type of nitrilium intermediates 258 and 259 are assumed to be formed by protonation of vinyl chlorides 255 by trifluoromethanesulfonic acid in the nitrile as a solvent (equation 7i)86133. The highly reactive vinyl cations 262 and 263 are generated from the vinyl triflates 261, obtained from corresponding ketones134. These cations react... 

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