Imines, alkylation tautomerism

Reactions of Halogenation and Nitrosation Nitrones with protons in the a-alkyl group can occur in tautomeric nitrone-hydroxylamine equilibrium (Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms. 

Pyridin-4-one, 1 -hydroxy-2,6-dimethyl-hydrogen-deuterium exchange reactions, 2, 196 Pyridin-4-one, 1-methyl-hydrogen-deuterium exchange, 2, 287 pK 2, 150 Pyridin-2-one imine tautomerism, 2, 158 Pyridin-2-one imine, 1-methyl-quaternization, 4, 503 Pyridin-4-one imine tautomerism, 2, 158 Pyridinone methides, 2, 331 tautomerism, 2, 158 Pyridinones acylation, 2, 352 alkylation, 2, 349 aromaticity, 2, 148 association... 

The 2-amino-selenazoles are crystalline compounds, and sometimes unstable, for example, the parent compound on heating in water undergoes complete decomposition. A few of these selenazoles which are substituted in the amino group are oily liquids. The basic character is more pronounced than in the alkyl- and aryl-selenazoles. The hydrochloride salts are, therefore, not so easily hydrolyzed in aqueous solution. 2-Amino- and 2-methylamino-4-methylselenazole have been considered to exist partly in the tautomeric selenazol-2-one imine form from comparison of their ultraviolet spectrum with that of 2-diethylamino-4-methylselenazole. ... 

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 tautomeric ratio of 25 in water for 5,6-dihydrocytosine should be compared with the value of 105 for cytosine itself (see Table II). It thus appears that the hydrogenation of cytosine causes a substantial shift toward the imine form. A further shift toward the imine is observed when 5,6-dihydrocytosine is substituted at the amino group by a hydroxy group. It was shown124 by UV spectra that 1-alkyl-substituted A4-hydroxy-5,6-dihydrocytosines exist in aqueous solution in the lactam(ox)imine form 20. 

Proton loss from cationic species of type (217 Scheme 116) can give rise to relatively stable imines which can be alkylated or acylated with some facility. However, imines are much more common in compounds which are not in tautomeric equilibrium with fully aromatic imidazoles, and among the imidazolidines. 

As described above, N-protected aromatic imines can be successfully employed as substrates for Mannich reactions. However, although N-protected alkyl imines constitute another important class of imine substrates, their instability hampers their use. N-protected alkyl imines are spontaneously tautomerized into the corresponding enamines even at low temperature. In aza-Henry (nitro-Mannich) reactions, this problem was overcome independently by Palomo [33a] and the group of Herrera, Bernardi, and Ricci [33b] by using the stable a-amidosulfones 73 from... 

KG113, 78KG843). It was found that whereas unsubstituted 2-aminoperimidine 94 (R1 = R2 = H) and its A-alkyl derivatives, e.g., 94 (R1 = H R2 = k-Bu), exist almost exclusively in the amino form 94a with the percentage of the imino tautomer not exceeding 5%, for A-acyl derivatives 94 (R1 = H, Me, Et R2 = MeCO, -PrCO, PhCO) the intramolecularly hydrogen-bonded tautomer 94b predominates. The complete shift of the tautomeric equilibrium to the imine tautomer 94b was observed for a-haloacyl-substituted aminoperimidines 94 (R1 = H R2 = ClCH2CO,... 

Chiral amines have been transformed into chiral imines RCH=NG, which are usually in equilibrium with the tautomeric enamines. These enamines undergo asymmetric alkylations, and the best results are often obtained with ethers 1.58 or with valine derivatives 1.59 (R = i-Pr, R = tert-Bu) [169, 173,253] in the presence of bases. Enamines, lithioenamines and zinc enamines derived from imines are very potent Michael donors that often participate in highly stereoselective reactions [161, 162, 169, 173, 254, 257, 260, 262, 267], Chiral imines can suffer very selective addition reactions of organomagnesium reagents [139, 253, 254] and allyl-metals [154, 258]. They also suffer stereoselective Ti-catalyzed silylcyanation [268], Strecker reaction [266], and [2+2] or [4+2] cydoadditions [131, 256, 263], When the reaction produces an imine product, the chiral auxiliary is recovered after acidic hydrolysis. However, when an amine is obtained as the product, as is often the case from phenethylamine derivatives, the chiral residue is cleaved by hy-drogenolysis. In such cases, the chiral amine is not, strictly speaking, a chiral auxiliary. But these processes will be discussed anyway because of their importance in asymmetric synthesis. 

Even though pteridinamines exist in their amino and not as their tautomeric imine forms, they usually alkylate on ring nitrogen, although the products may undergo subsequent Dimroth rearrangement274 276 to yield alkylaminopteridines. However, trimethylsilylation normally results in the formation of (trimethylsilylamino)pteridines directly (see Section 7.3.1.4.3.1.). 

---