Nitrilimines. cycloaddition

Mannich reaction of A, A -bis(methoxymethyl)diaza-18-crown-6 with 4-chloro-2-(l/f-pyrazol-3-yl)phenol gave the N-linked bis(3-(5-chloro-2-hydroxy)pyrazol-l-ylmethyl)-substituted diazacrown ether, which interacted with various metal ions and was evaluated by calorimetric titration <1999JOC8855>. Intramolecular nitrilimine cycloadditions were exploited in the preparation of a number of azacrown ethers having a medium or large ring annulated to pyrazole units <1997T3005>. 

Intramolecular nitrilimine cycloadditions gave new pyrazolo[4,3-c]pyrrolizines 50 <04H(63)1423>. The syntheses of 5-substituted ethyl 3-oxo-2/7-pyrazolo[4,3-c]pyridlne-7-carboxylates 51 <04H(63)609> and 5//-pyrazolo[4,3-c]quinolines 52 <04H(63)1883> have been described. Ring-closure reactions of 3-arylhydrazonoalkyl-quinolin-2-ones gave rise to 1-aryl-pyrazolo[4,3-c]quinolin-2-ones <04JHC681>. 

Molteni G (2004) Synthesis of the new pyrazolo[4,3-c]pyrrolizine skeleton via intramolecular nitrilimine cycloaddition. Heterocycles 63 1423-1428 52. Padwa A, Hertzog DL et al (1994) Studies on the intramolecular cycloaddition reaction of mesoionics derived from the rhodium(II)-catalyzed cyclization of diazoimides. J Org Chem 59 1418-1427... 

Molteni G, Orlandi M, Broggini G (2000) Nitrilimine cycloadditions in aqueous media. J Chem Soc Perkin Trans 1 3742-3745... 

The reaction is illustrated by the intramolecular cycloaddition of the nitrilimine (374) with the alkenic double bond separated from the dipole by three methylene units. The nitrilimine (374) was generated photochemically from the corresponding tetrazole (373) and the pyrrolidino[l,2-6]pyrazoline (375) was obtained in high yield 82JOC4256). Applications of a variety of these reactions will be found in Chapter 4.36. Other aspects of intramolecular 1,3-dipolar cycloadditions leading to complex, fused systems, especially when the 1,3-dipole and the dipolarophile are substituted into a benzene ring in the ortho positions, have been described (76AG(E)123). 

Nitrilimines can be produced by treating halogenated hydrazones with a base such as triethylamine. These nitrilimines undergo 1,3 cycloaddition with enamines to form pyrazoles (181-183). This is shown by the reaction of the pyrrolidine enamine of cyclohexanone with diphenyinitrilimine to... 

In general, nitrilimines are generated in the presence of a suitable dipo-larophile. Thus, heating an equimolar mixture of hydrazone 313, alkene 314, and chloramine-T trihydrate in ethanol under reflux for 3 h provided pyrazolines 315 in 68-90% yield [81]. The cycloaddition in all the cases was regiospecific as indicated by NMR (Table 23). 

The cycloaddition between a nitrilimine 319 and an aroyl substituted heterocyclic ketene aminal 318 has been found to be stepwise, involving an initial nucleophilic addition of 318 to 319 followed by intramolecular cyclocondensation of the intermediate 320 providing fully substituted pyrazole 321 (Eq. 36) [92]. When Ar was the 2,4-dinitrophenyl group, the intermediate 320 was isolable and required forcing conditions (xylene, reflux, 10 h) to undergo cyclization ... 

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>. 

Table 20 Cycloaddition reaction of in s/ fu-generated nitrilimines with nitriles to give 1,3,5-trisubstituted 1,2,4-triazole derivatives (Equation 37)...

A diastereoselective synthesis of bis(3,5)pyrazolophanes was accomplished by sequential inter- and intramolecular cycloadditions of homochiral nitrilimine intermediates . A-Alkyl pyrazolidine-3,5-diones were synthesized in a three-step sequence from dialkyl malonates <00JHC1209>. Methyl acetoacetate was employed as the initial substrate to 3-carboxamido-4-pyrazolecatboxylic acid derivatives <00JHC175>. Vilsmeier type reagent 33 reacted with imines 34 to afford enaminoimine hydrochlorides 35, which were transformed to pyrazoles 36 upon addition of hydrazine <0OJHC13O9>. 

The cycloaddition of nitrilimines toward furo[3,4-c]thieno[2,3-r7]-pyrazoles has been investigated as a function of the electron-withdrawing or electron-donating character of the substituents attached to the aromatic rings <2000H(53)917>. For instance, nitrilimine 459, obtained in situ from hydrazonoyl chloride 458, by base treatment with silver carbonate in dioxane, when reacted with 460, gives a mixture of compounds 461 and 63 (Scheme 53) <2000H(53)917>. 

A 1,3-dipolar cycloaddition approach to this group of compounds involving reaction of a nitrilimine and C=N bond have already been mentioned in CHEC-II(1996) <1996CHEC-II(8)421>. Such a transformation has recently been elaborated by an English team <1994J(P1)3563> for the ring closure of the partially saturated oxazine 287 with nitrile oxide to yield the bicyclic product 288 in medium yield (42%). 

In 1981 we published the first paper [22] on the synthesis of s-triazolo[4,3-a]pyridinium salts, 4, by the anodic oxidation of hydrazones 3 in the presence of pyridine (Scheme 5). In our working mechanistic scheme we proposed nitrilimine as the possible intermediate and pointed out that this reaction opens the door to a wide range of heterocyclic systems via anodic oxidation of aldehyde hydrazones through 1,3-dipolar cycloaddition reactions of the nitrilimine involved. 

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