Azides azomethines with

Organic azides react with alkenes via 1,3-dipolar cycloaddition The resulting 1,2,3-triazolines are thermally unstable and eliminate nitrogen, to give azomethines (equation 5) beside other products such as aziridines. 

Azides, reaction with thiols 752 Azodkarboxylic acid, diethyl ester, oxidation of thiols by 799 Azomethine bond, addition of thiols 765... 

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

For intramolecular 1,3-dipolar cycloadditions, the application of nitrones and nitrile oxides is by far most common. However, in increasing frequency, cases intramolecular reactions of azomethine ylides (76,77,242-246) and azides (247-259) are being reported. The previously described intermolecular approach developed by Harwood and co-workers (76,77) has been extended to also include intramolecular reactions. The reaction of the chiral template 147 with the alkenyl aldehyde 148 led to the formation of the azomethine ylide 149, which underwent an intramolecular 1,3-dipolar cycloaddition to furnish 150 (Scheme 12.49). The reaction was found to proceed with high diastereoselectivity, as only one diaster-eomer of 150 was formed. By a reduction of 150, the proline derivative 151 was obtained. 

Whereas aryl, acyl, and sulfonyl azides decompose in the presence of aluminum trichloride in benzene solution only with evolution of N , alkyl azides also split oif significant amounts of N,-.1 -18 At 50° alkylbenzenes and azomethines are obtained. In order to explain these results, Kreher and Jager suggested that two intermediate complexes may be formed (Scheme IV). According to Goubeau, Allenstein, and... 

Ir and nmr analysis of the condensation products of primary amines with aldehydes and ketones are in favor of the Schiff-base structure (46a). Nevertheless, these substances react with aryl azides in chloroform solution in the tautomeric enamine form (46b) yielding aminotriaiolines.206 225- 227 It proves that the dipolarophilic activity of an enamine olefin bond is much greater than that of an azomethine bond. 

Perfluoroalkyl-substituted nitriles react readily with various 1,3 dipoles, such as azomethine ylides [755,156,157],azometlune imines [158],diazoalkanes [759],azides [160 161,162], and nitrile ylides [163] to give stable five-membered ring systems (equation 37)... 

Triazolines bearing three electron-withdrawing groups (Scheme 85) undergo complex thermolysis reactions. Aziridine formation is observed but sometimes the azide cycloreversion operates pyrrolidines are thus formed by reaction of the olefins with the azomethine ylides from the aziridines. The aziridines also dimerize to piperazines under the conditions of thermolysis.446... 

Ultraviolet irradiation of mesityl azide 288 in the presence of tetracyanoethylene has resulted in the isolation of the intermediate azomethine ylide 289 (from trapping of the aryl nitrene) together with its rearrangement product, the spiroazepine 290 (Scheme 36) <1997JOC3055>. Photolysis (at 313 nm) at low temperature of 1- and 2-azido-naphthalenes in an Ar matrix provided access to the novel seven-membered cyclic ketenimines 291 and 292, respectively <2004JA237>. 

In many cases N-substitued anilines or azomethines (resp. enamines) react with two equivalents of diethyl malonate to give pyrono derivatives of 2-quinolones or 2-pyridones in good yield [84JHC1881] [89JHC1555] [88TH000] [90THO00], Chlorination of these compounds with sulfuryl chloride and aqueous work up yields dichloroacetyl derivatives of quinolones and pyridones which in turn react with sodium azide to afford a variety of diazidoacetyl derivatives of type 38. 

As mentioned above, the quaternarization method using N-silylmethyl-imines [Eq. (2)] offers an even more general and convenient method of azomethine ylide generation than the original N-silylmethylation method shown by Eq. (1). Another advantage is the ready availability of N-silylmethylimines, which are conveniently prepared by the condensation of carbonyl compounds with silylmethylamine or with silylmethyl azide in the presence of triphenylphosphine (84JOC2688). 

Azomethines have also been obtained in the reaction of azides with thioketones. Thiobenzephenone and phenyl azide thus yielded ben-zophenone anil (72), probably via the cyclic intermediate 71 . ... 

Although thermolysis of triazoline can also, in certain cases , lead to aziridines, mixtures with azomethines usually result, and the photochemical process is preferable. The triazolines formed from acyl ° or sulphonyl azides are unstable and the corresponding aziridines can be obtained directly. The reaction of norbomene and benzoyl azide at 40° yielded the aziridine (128) directly... 

Electron-rich double bonds also show very high reactivity. En-amines react very readily with azides yielding 1-substituted 5-amino-1,2,3-triazoHnes . The orientation is determined by electronic rather than steric effects. The piperidine enamines of acetophenone (231) and phenyl acetaldehyde (233) yielded the isomeric triazolines 232 and 2 respectively . Azomethines also react in the form of enamines, yielding aminotriazolines. The reaction of -propylidene-... 

When the azomethine group is part of an electron-deficient ring, such as pyridine, pyrimidine or thiazole, the compounds exist as tetrazoles in the solid state, and at equilibrium with the azido form in solution . The equilibrium constants depend on the solvent, the nature of the substituents and the temperature . 2-Azido-4,6-dimethylpyrimidine (288a) thus exists in equilibrium with tetrazolo-pyrimidine (288b). Its chemical behaviour is, however, in accord with the azide structure 288a, including dipolar addition reactions and nitrene reactions . 

Using diazoalkanes results in the formation of isomeric mixtures of cycloadducts.Unlike some reactants (phenyl azide, tosyl azide and diphenylnitrilimine), benzonitrile oxide, diazomethane, and A-phenylbenzylideneamine A-oxide underwent [3 4- 2] cycloaddition on mixing with lumisantonin using A -phenylbenzylideneamine A-oxide, however, gave the product cycloadduct in 8% yield.Dihydropyrazoles were obtained in some cases.Furthermore, pyrrole derivatives were obtained in low yield by intramolecular addition of an azomethine ylide to an a- and / -monocyclopropyl acrylate moiety. 

The influence of water as a solvent on the rate of dipolar cycloadditions has been reported [76]. Thus the rate of the 1,3-dipolar cycloaddition of 2,6-dichloroben-zonitrile N-oxide with 2,5-dimethyl-p-benzoquinone in an ethanol/water mixture (60 40) is 14-fold that in chloroform [76b]. Furthermore the use of aqueous solvent facilitates the workup procedure owing to the low solubility of the cycloadduct [76b]. In water-rich solutions, acceleration should be even more important. Thus in water containing 1 mol% of l-cyclohexyl-2-pyrrolidinone an unprecedented increase in the rate of the 1,3-dipolar cycloaddition of phenyl azide to norbornene by a factor of 53 (relative to hexane) is observed [77]. Likewise, the 1,3-dipolar cycloaddition of C,Ar-diphenylnitrone with methyl acrylate is considerably faster in water than in benzene [78]. Similarly, azomethine ylides generated from sarcosine and aqueous formaldehyde can be trapped by dipola-rophiles such as N-ethylmaleimide to provide pyrrolidines in excellent yields... 

Dipoles always contain a heteroatom as the central atom of the trio, either sp or sp hybridised. Amongst other examples, cycloadditions have been demonstrated with azides (N=N -N-R), nitrile oxides (R-C N -0 ) and nitrile ylides (R-C N -C Ra), where the central atom is sp-hybridised lutrogen, and with nitrones (R2C=N" (R)-0 ), carbonyl ylides (R2C=0 -C R2) and azomethine ylides (R2C=N (R)-C R2), where the central atom is sp hybridised. 

The following 1,3-dipoles will be considered (a) aryl azides (b) diazoalkanes (c) aryl nitrile oxides (d) nitrile imines (e) azomethine imines (/) azomethine oxides (g) azomethine ylides. (a) to (d) represent 1,3-dipoles with a double bond in their sextet structure, while the last three, from (e) to (g), are without a double bond . All of them have nitrogen as the central atom of the 1,3-dipole. They will be formulated as allyl-like systems, having their negative charge distributed (according to an unspecified balance) at the two sides of the positive nitrogen, e.g. 

Cycloadditions were found to be first-order reactions with respect to both 1,3-dipole and dipolarophile, in all cases so far investigated. There are some limits to kinetic studies of these reactions, as many 1,3-dipoles are very reactive substances. While aryl azides, diazoalkanes, some classes of azomethine imines (for instance sydnones), and some classes of azomethine oxides (nitrones) are stable and isolable, azomethine ylides are usually unstable, an exception being represented by a mesoionic oxazolone that has been used for kinetic investigations benzonitrile oxide has a very limited stability, although some substituted derivatives are stable for long periods nitrile imines are not commonly isolable because of their strong tendency to dimerise. 1,3-Dipoles of... 

If one uses dipolarophiles with carbon-carbon unsaturated bonds, when the difference in energy of the two possible products is less marked, the orientation often is specifically determined by the type of 1,3-dipole and does not depend on the polarity of the dipolarophile (i). This proves that we are not dealing simply with polar reactions. Sensitivity of orientation to the nature of the substituent Y appears in case (ii) where the intrinsic difference between atoms I and 3 of the 1,3-dipole is attenuated, as for azides and apparently also for azomethine imines both classes of 1,3-dipoles show some basically similar responsiveness of atoms I and 3, by presenting cases of double orientation (in). Such cases are relatively rare for 1,3-cycloadditions with monosubstituted dipolarophiles however, the situation is more complex in the case of disub-stituted olefins. ... 

The consensus of opinion on the formation of azepines from aryl azides suggests that an intermediate singlet nitrene is in equilibrium with a didehydroazepine, which itself may be in equilibrium with a azepinocarbene. This has received further support form the investigations of Murata and co-workers, who have isolated both the azomethine ylide 1 and the... 

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