Detection imine formation

Imines readily hydrolyze under basic or acidic conditions. Figure 52 shows the acid-catalyzed hydrolysis of imines. When developing methods to detect imines, it is often necessary to use neutral pH conditions to optimize the stability of the imine. An example of imine formation and hydrolysis is found in the degradation chemistry of the API sertraline hydrochloride (Fig. 53) (86). 

Dunkin and Thomson studied the photochemistry of tert-butyl azide (4) in an Ng matrix at 12 K. Using IR spectroscopy, they detected the formation of only one product — imine 5. 

The reaction was shown to follow step-growth kinetics in its early stages and to stop abruptly at the length defined by the template. No products were detected in the absence of any template. As the hydrogen bonding between the nucleobases and the imine formation are reversible, error correction occurs to some extent in this system. In this sense, this report matches the spirit of DCC more closely than many others. Unfortunately, no follow-up using the entire nucleic acid alphabet has been published hitherto. 

The precise structure of the zirconium catalyst was examined by NMR analysis. When Zr(Ot-Bu)4 (1 equiv), 8b (2 equiv), and NMI (3 equiv.) were combined in benzene-dg at 23 °C, two independent species which were assigned to a new zirconium catalyst and free 8b were observed. Although the signals of free 8b were still observed when Zr(Ot-Bu)4 (1 equiv), 8b (1 equiv), and NMI (3 equiv.) were stirred at 23 °C, only the signals assigned to the new zirconium catalyst were detected when the mixture was stirred at 80 °C for 2.5 h. These results indicated the formation of 9b as the new zirconium catalyst. The structure was also supported by an experiment in which Zr(Ot-Bu)4 (0.2 equiv), 8a (0.2 equiv), NMI (0.6 equiv), and MS 3 A were combined in benzene and the mixture was stirred for 2.5 h at 80 °C (formation of 9a). Imine Id (1 equiv.) and 7a (1.2 equiv.) were then added to the catalyst solution, and the mixture was stirred for 48 h at 23 °C. After the same work-up procedures as described above, the desired piperidine derivative was obtained in >98% yield with 89% ee, values comparable with those... 

Both compounds 190 and 193 are reduced to 9,10-diphenylanthracene (205) by zinc and acetic acid. However, more interest attaches to the formation of anthracenes from anthracen-9,10-imines in nonreducing conditions. The iV-ethoxycarbonyl derivative (192) decomposed at 215° in cyclohexane to 33% of 205, although curiously this product was not obtained if the solvent was previously degassed. Whether or not the reaction involves simple extrusion of ethoxycarbonyl nitrene could not be established, since the expected iV-cyclohexylurethane was not detected. The 9,10-epithioanthracene (194) loses sulfur thermally to give 205. ... 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

The reactions were conducted in the liquid phase at conditions described in the experimental section. Test reactions were conducted to establish that the reactions were kinetically limited. In cases where the rate of reaction was >5 mmoP(g min), the selectivity to 6-PPD was >97% and the yield of 6-PPD was >96%. Hence, the rate of hydrogen uptake was taken to be directly proportional to the formation of 6-PPD. This rate calculated at constant temperature and conversion was normalized to the amount of catalyst used and is shown in column 6 of Tablel. The two cases where Pt/S ratio was high (Run 3 4), hydrogenation of the ketone (MIBK) to the alcohol, methyl isobutyl carbinol (MIBC), was observed. In cases where the Pt/S ratio was low (Run 5 6), significant amounts of the imine was detected in the GC. 

To suppress enamine-derived side products, we explored addition of benzotriazole (BtH) to the reaction mixture. The premise behind these experiments was the ability of BtH to form stable adducts with imines,23,24 thereby blocking tautomerization of 19 to 20 through in situ formation of the benzotriazolyl derivative 21. It was hoped that subsequent hydride displacement of the Bt moiety would afford the desired mono alkylated products 23. Indeed, analytical high-performance liquid chromatography (HPLC) revealed a remarkable improvement in terms of product purity, especially for reactions carried out at room temperature, with the desired secondary anilines 23 being essentially the only products detected. In... 

The basicity of the amine nitrogen appears to be an important factor for an effective asymmetric induction. Phenyl substituents on the nitrogen atom greatly retard the reaction rate. Thus, /V-phenyl- and IV.lV-diphenylgeranylamine are inert at 40°C and 24 h reaction time. Few characteristic features are worth noting. If an allylamine is secondary, the product is the corresponding imine, a more stable valence tautomer of the enamine, which cannot be detected in the reaction mixture. The exclusive formation of an ( )-enamine regardless of the double-... 

The influence of both anti and syn substitution in the 10-position on the thermolysis of triazoline adducts from a number of 7-substituted norbornenes (Scheme 14) has been investigated.128 Both the anti- and syn-substituted triazolines give only the exo-aziridine upon photolysis but pyrolysis yields endo-aziridines from the syn- and exo-aziridines from the anti compounds. The syn substituents have a strong endo directing influence and no exo-aziridine is detected in any case. Ketone formation in some cases apparently results from hydrolysis of the imines during workup.128... 

Staudinger reaction of imine 8 derived from 7-oxanorbomenone with 2-alkoxy-acetyl chlorides in the presence of Et3N (toluene, RT), afforded (3-lactams 9 (Scheme 3). These were obtained as single diastereomers, and no traces of the corresponding isomeric exo-(3-lactams were detected in the crude reaction products [50]. It is worth mentioning that this stereochemical outcome of (3-lactam formation with acid chlorides under Staudinger reaction conditions was opposite to the one expected from a simple [2+2]-cycloaddition reaction, which should have taken place from the exo face of compound 8. 

Reaction of 9-[chloro(dimethylamino)methylene]tetrahydropyrido[l, 2-a]pyrimidin-4-ones 608 and aldimines or ketimines 609 in chloroform and acetonitrile gave a diastereomeric mixture of tricyclic compounds 611 and 612 at room temperature (82BEP892120, 82TL2891). The formation of compound 610 and the formation of a 1 1 mixture of the tricyclic products 611 and 612 could be detected by H NMR spectroscopy (82TL2891). After refluxing the reaction mixtures, only the thermodynamic product 611 could be isolated in pure form. 9-[Chloro(dimethylamino)methylene] derivatives 608 (R = CN, COOEt) also reacted with cyclic imines to yield the corresponding tetra- and pentacyclic quaternary salts, similar to 611 and 612 (87H2615). 

These findings confirmed that glyoxal dicyclohexylimine is one of the products from the reaction of glucose with cyclohexylamine in ethanol. Although the formation of similar imines by the reaction of glucose with other alkylamines was not directly established, detection of glyoxal by silica gel TLC, shown in Fig. 9, in all of these cases seems to justify the assumption that the two-carbon diimines are always among the products of this kind of reaction, under the conditions employed. 

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