Imines anions

The carbon-nitrogen double bond in imines is reduced at less negative potentials than the corresponding carbonyl function. Also imine radical-anions are more basic than carbonyl radical-anions. Imines with at least one phenyl substituent on the carbon-nitrogen double bond are sufficiently stable for examination in aprotic solvents and reversible one-electron reduction of benzaldehyde anil [179] or benzophenone anil [ISO] can be demonstrated with rigorous exclusion of moisture. 

Strong nucleophiles, such as organometallic reagents, add to nitriles to give anionic imine salts. Work-up with aqueous acid gives the neutral imine, which is rapidly hydrolyzed to the ketone (Section 17-9). 

Acid Dyes. These water-soluble anionic dyes ate appHed to nylon, wool, sUk, and modified acryHcs. They ate also used to some extent for paper, leather, food, and cosmetics. The original members of this class aU had one or mote sulfonic or catboxyHc acid groups in thein molecules. This characteristic probably gave the class its name. Chemically, the acid dyes consist of azo (including preformed metal complexes), anthraquiaone, and ttiaryHnethane compounds with a few azHie, xanthene, ketone imine, nitro, nitroso, and quHiophthalone compounds. 

The reactions of ketenes or ketene equivalents with imines, discussed above, all involve the imine acting as nucleophile. Azetidin-2-ones can also be produced by nucleophilic attack of enolate anions derived from the acetic acid derivative on the electrophilic carbon of the imine followed by cyclization. The reaction of Reformatsky reagents, for example... 

The Jackson modification involves cyclisation of iV-tosylated amine 12 and provides a complementary method to the classical Pomeranz-Fritsch reaction for entry into the fully unsaturated ring system 13. Amine 12 can be prepared from either the Pomeranz-Fritsch-Bobbitt imine 10 or reaction of benzylhalide 14 and the corresponding sodium anion 15. ... 

Only in 1961 did Woodward and Olofson succeed in elucidating the true mechanism of this interesting reaction by making an extensive use of spectroscopic methods. The difficulty was that the reaction proceeds in many stages. The isomeric compounds formed thereby are extremely labile, readily interconvertible, and can be identified only spectroscopically. The authors found that the attack by the anion eliminates the proton at C-3 (147) subsequent cleavage of the N—0 bond yields a -oxoketene imine (148) whose formation was established for the first time. The oxoketene imine spontaneously adds acetic acid and is converted via two intermediates (149, 150) to an enol acetate (151) whose structure was determined by UV spectra. Finally the enol acetate readily yields the W-acyl derivative (152). 

In a further development on this theme, the thiol, 153, is first alkylated to the corresponding benzyl ether (158). Treatment with sodium methoxide removes the proton on the amide nitrogen to afford the ambient anion (159). This undergoes alkylation with methyl bromide on the ring nitrogen thus it locks amide into the imine form (160). Chlorolysis serves both to oxidize the sulfur to the sulfone stage and to cleave the benzyl ether linkage there is thus obtained the sulfonyl chloride, 161. 

Ornithine decarboxylase is a pyridoxal dependent enzyme. In its catalytic cycle, it normally converts ornithine (7) to putrisine by decarboxylation. If it starts the process with eflornithine instead, the key imine anion (11) produced by decarboxylation can either alkylate the enzyme directly by displacement of either fluorine atom or it can eject a fluorine atom to produce viny-logue 12 which can alkylate the enzyme by conjugate addidon. In either case, 13 results in which the active site of the enzyme is alkylated and unable to continue processing substrate. The net result is a downturn in the synthesis of cellular polyamine production and a decrease in growth rate. Eflornithine is described as being useful in the treatment of benign prostatic hyperplasia, as an antiprotozoal or an antineoplastic substance [3,4]. 

Like a carbonyl group, a nitrile group is strongly polarized and has an electrophilic carbon atom. Nitriles therefore react with nucleophiles to yield 5p2-hybridized imine anions in a reaction analogous to the formation of an sp3-hybridized alkoxide ion by nucleophilic addition to a carbonyl group. 

Base catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide ion to the polar C N bond to give an imine anion in a process similar to nucleophilic addition to a polar C=0 bond to give an alkoxide anion. Protonation then gives a hydroxy imine, which tautomerizes (Section 8.4) to an amide in a step similar to the tautomerization of an enol to a ketone. The mechanism is shown in Figure 20.4. 

O Nucleophilic addition of hydroxide ion to the CN triple bond gives an imine anion addition product. 

Protonation of the imine anion by water yields a hydroxyimine and regenerates the base catalyst. 

Reduction Conversion of Nitriles into Amines Reduction of a nitrile with LiAIH4 gives a primary amine, RNH . The reaction occurs by nucleophilic addition of hydride ion to the polar C=N bond, yielding an imine anion, which still contains a C=N bond and therefore undergoes a second nucleophilic addition of hydride to give a dianion. Both monoanion and dianion intermediates are undoubtedly stabilized by Lewis acid-base complexafion to an aluminum species, facilitating the second addition that would otherwise be difficult Protonation of the dianion by addition of water in a subsequent step gives the amine. 

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

Unlike the parent system, 5-methyl-5//-dibenz[c,e]azepine (1, R1 = Me R2 = H) on treatment with lithium diisopropyl amide fails to yield the tautomeric phenanthridine-imine (see Section 3.2.1.5.4.2.), but forms the 5-carbanion, which on quenching with deuterium oxide furnishes 5-methyl-[5-2H,]-5//-dibenz[e,e]azepine (l).83 5,7-Diphenyl-5//-dibenz[r,e]azepine (1. R1 = R2 = Ph) behaves similarly. In contrast, however, 5,7-dimethyl-5//-dibcnz[c,e]azepine (1, R1 = R2 = Me) yields theazaallyl anion 3, which on addition of deuterium oxide deuterates regiospecifically at the 7-methyl group to give derivative 4. 

Davis has also employed a similar procedure for the synthesis of aziridine-2-phosphonoates, involving the addition of N-(2,4,6-trimethylphenylsulfinyl)imine to anions of diethyl a-halomethyl phosphonates (Scheme 1.29) [53, 54], Aziridines... 

Finally, an intramolecular reaction of an oxygen nucleophile to give 2,5-dihy-drofuran derivatives 146 is shown in Scheme 2.37. Since the vinylaziridines were generated in situ by treatment of imines 143 with ylide 144, this ylide is formally acting as an equivalent of the 2,5-dihydrofuran anion [57]. 

Lithium and zinc tert-butyl phenylmethyl sulfoxide (1) and A-phenyl imines 2, in which the substituent R is alkenyl or aryl, react at —78 °C over 2 hours with high anti diastereoselection (d.r. >98.5 1.5)6. Shorter reaction times result in poorer yields, due to incomplete reaction. In contrast, the reaction of the sulfoxide anion with benzaldehyde is complete after 5 seconds, but shows poor diastereoselection. When the substituent R1 or R2 of the imine 2 is aliphatic, the substrates exhibit poor chemical reactivity and diastereoselection. The high anti diastereoselection suggests that if a chelated cyclic transition state is involved (E configuration of the imine), then the boat transition state 4 is favored over its chair counterpart 5. 

In general, metalated 2-azaallyl anions derived from imines of a-amino esters serve both as Michael donors and as 1,3-dipolar reagents the course of the reaction, as well as the stereochemical outcome depends upon the base and the reaction conditions82,83. 

Ethyl (bornylideneamino)acetate (2) and the imines of (-)-(lf ,2, 5 )-2-hydroxy-3-pinanone and glycine, alanine and norvaline methyl esters were particularly successful as Michael donors. The chiral azaallyl anions, derived from these imines by deprotonation with lithium diisopropylamide in THF at — 80 C, add to various a,/i-unsaturated esters with modest to high diastereoselectivity (see Section 1.5.2.4.2.2.5.). Thus, starting with the imine 2, (R1 = CH,) and ethyl ( )-2-butcnoate, the a,/i-dialkylated glutamate derivative 3 is obtained as a single diastercomer in 90% yield91-92. 

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