Amines, cyclic azomethines

The measurement of circular dichroism is an especially sensitive and excellent method for studying the reactions of 34. A freshly prepared solution of 34 at pH 7.8 contains no 33 or 22 after several hours, a Cotton effect is observable, and it attains a maximum after two days. Thus, the equilibrium 34 33 has been established. The position of the equilibrium is dependent on the pH at pH 7.8, the content of 33 is 3—6%, on the assumption that 33 has a molar extinction coefficient of circular dichroism similar to that found for other cyclic azomethines. On treatment of the solution with carbon dioxide to pH 6.8, the Cotton effect disappears immediately, because the acid-catalyzed Amadori rearrangement of 33(= 16) —> 22 is accelerated. Compound 22 is, however, a secondary amine, and is a stronger base than 33 and 34, so that the continued formation of 22 causes ftie pH to rise. Thereby, the acid-catalyzed Amadori rearrangement is slowed down so much that the equilibrium 33 34, with its high Cotton... 

From a synthetic viewpoint, iV-arylvinylamines are not appropriate as azomethine ylide precursors because the hydrogen shift from the intermediary ylides must be extremely accelerated by the rearomatization of the fused dihydro benzo moiety. Zaima and Mitsuhashi were the first to succeed with synthetic applications of the above photochemical generation method of cyclic azomethine ylides (83JHC1). The substrate employed in their work is bis(l-methoxycarbonylvinyl)amine. Irradiation of this divinylamine in carbon tetrachloride at 18°C in the presence of acetylenedicarboxylates produces excellent yields of 7-azabicyclo[2.2.1]hept-2-ene-l,2,3,4-tetracarboxylates 172, which correspond to the cycloadducts of the expected azomethine ylide intermediate 171. Heating the bicyclic cycloadducts 172 at 90-120°C induces a smooth cycloreversion eliminating a molecule of ethene to give pyrrole-2,3,4,5-tetracarboxylates in quantitative yields. The azomethine ylide 171 can be trapped also with olehnic dipolarophiles, such as maleates and fuma-rates, to furnish stereospecifically 7-azabicyclo [2.2.1] heptane-1,2,3,4-tetra-carboxylates 173 and 174, respectively (84JHC445). 

Lactams from cyclic amines. A mixture of iodosobenzene and water stirred for 15 min, the slurry cooled to 0°, treated in one portion with pyrrolidine, stirred at 9" for 1 h, then at room temp, until a clear soln. was obtained (4-5 h) - 2-pyrrolidinone. Y 49%. F.e. inch 3,4-dihydroisocarbostyrils and 2-piperidones, also nitriles from prim, amines, and cyclic ketones from cycloalkylamines, s. R.M. Moriarty et al., Tetrahedron Letters 29, 6913-6 (1988) cyclic azomethines in methylene chloride cf. ibid. 6917-20. 

Silver nitrate sodium hydroxide Cyclic azomethines from cyclic sec. amines... 

Cyclic tert. amines from cyclic azomethines... 

Chen extended the scope of his iminium ion catalysed [3+2] cycloaddition with azomethine imines (see Sect. 2.1.2) to encompass cyclic a,P-unsaturated ketone substrates using primary amine 147 as the catalyst [194]. Interestingly, the presence... 

Aryl alkyl amines gave hydroxylamine 0-arylsulfonates when reacted with arylsul-fonyl peroxide. The products were later decomposed to azomethine and further hydrolysis results in the corresponding amine with one less carbon atom. Thus when p-methoxy-benzylamine was treated with p-nitrophenylsulfonyl peroxide at —78 °C in ethyl acetate, p-methoxybenzaldehyde and p-methoxyaniline were obtained . Cyclic amines with p-nitrophenylsulfonyl peroxide were converted to the Al-(p-nitrophenylsulfonyloxy)amine derivatives, which further rearranged to ring-expanded cyclic imines in good yields (equation 9 f. ... 

Synthetic and biological interest in highly functionalized acyclic and cyclic amines has contributed to the wealth of experimental methodology developed for the addition of carbanions to the caibon-mtrogen double bond of imines/imine derivatives (azomethines). While a variety of practical methods exist for the enantio- and stereo-selective syntheses of substituted alcohols from aldehyde and ketone precursors, related imine additions have inherent structural limitations. Nonetheless imines, by virtue of nitrogen substitution, add a synthetic dimension not available to ketones. In addition, improved procedures for the preparation and activation of imines/imine derivatives have increased the scope of the imine addition reaction. 

A year later, based on the same principle by using primary amine-catalyzed iminium ion activation in combination with external Brpnsted acid additives, Chen et al. [129] were able to achieve the asymmetric 1,3-dipolar cycloaddition of cyclic enones and a variety of azomethine imines in excellent yields and selectivities (Scheme 11.48). In this case, to scavenge the generated H2O during the formation of the enamine nucleophile intermediate, and to overcome the expected hydrogenbonding interaction, a stoichiometric amount of molecular sieves (4 A) was added. Interestingly, when the pseudoenantiomer catalyst 61 was employed, an opposite enantiomer of the product was formed in good yields and selectivities. 

Schiff bases s. Azomethines Schlotterbeck s. Buchner Schmidt reaction 17, 524 —, amines from carboxylic acids 19, 305 20, 366 —, lactams from ketones, cyclic, ring expansion... 

C=N—, linkage and water. The reaction of carbonyl compounds with secondary and tertiary amines generally does not result in the formation of an azomethine linkage. Carbonyl compounds having an a-hydrogen atom react with secondary amines to give enamines. When, however, the perchlorate salts of the secondary amines are employed, ternary iminium salts are obtained . The reaction of certain cyclic ketones with tertiary amines at low temperatures results in unstable complex formation. ... 

Azomethines derived from formaldehyde are cyclic aminals, (RN=CH2)3, and in their reaction with alkyl isothiocyanate, [2+2+2] cycloadducts are obtained as result of an insertion into the C-N bond of the cyclic aminal. ... 

Although considerable improvements have been made for endo-selective cycloadditions of azomethine imines, methods for exo and enantioselective cycloaddition of azomethine imines were relatively scarce. By employing novel, multifunctional primary amine catalysts 145 derived from cinchona alkaloids in the presence of triisopropylbenzene sulfonic acid (TIPBA) 146 as cocatalyst, Chen and coworkers developed the first organocatalytic, highly exo-selective, and enantioselective 1,3-DC reaction of cyclic enones 142 and azomethine imines 143 in 2007 [53]. The additional and synergistic hydrogen-bonding interaction of catalyst and 1,3-dipole is essential for enantiocontrol, and excellent stereoselectivities were achieved for a broad scope of substrates (dr > 99 1, up to 95% ee) (Scheme 2.37). 

A stereoselective [3+2] dipolar cycloaddition of azomethine imines 141 with ot,P-unsaturated aldehydes catalyzed by ot,a-diarylprolinol salts was also reported by Chen et al. [88]. More important, they extended the strategy to cyclic enones by employing a Cinchona alkaloid-derived bifunctional primary amine catalyst 142 (Scheme 1.52) [89]. The synergistic hydrogen-bonding interaction of the catalyst and 1,3-dipoles 141 plays a critical role in high enantiocontrol (dr >99 1, up to 95% ee). 

---