Imine salts from amines

The mechanism involves the preliminary formation of an imine salt from the amine and formaldehyde. The amine is nucleophilic and attacks the more electrophilic of the two carbonyl compounds available. That is, of course, formaldehyde. No acid is needed for this addition step, but acid-catalysed dehydration of the addition product gives the imine salt. In the normal Mannich reaction, this is just an intermediate but it is quite stable and the corresponding iodide is sold as Eschenmoser s salt for use in Mannich reactions. 

Polyamines can also be made by reaction of ethylene dichloride with amines (18). Products of this type are sometimes formed as by-products in the manufacture of amines. A third type of polyamine is polyethyleneimine [9002-98-6] which can be made by several routes the most frequently used method is the polymeriza tion of azitidine [151 -56 ] (18,26). The process can be adjusted to vary the amount of branching (see Imines, cyclic). Polyamines are considerably lower in molecular weight compared to acrylamide polymers, and therefore their solution viscosities are much lower. They are sold commercially as viscous solutions containing 1—20% polymer, and also any by-product salts from the polymerization reaction. The charge on polyamines depends on the pH of the medium. They can be quaternized to make their charge independent of pH (18). 

Spelling of amonium, imonium, and iminium indicates derivation from amine and imine onium salts. 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

CuOTf/PyBox System The first direct asymmetric addition of alkynes to imines, generated from aldehydes and amines in situ, was reported by using copper salts in the presence of chiral PyBox ligand (Scheme 5.2). The products were obtained in good yields and excellent enantioselectivities in most cases. When toluene was used as solvent, up to 93% yield and 99% ee were obtained. Up to 99.5% ee was obtained when the reaction was carried out in 1,2-dichloroethane. The reaction can also be performed in water smoothly, and good enantioselectivities (78-91% ee) were obtained. 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

Mukaiyama and coworkers have pioneered many routes to the total syntheses of rare carbohydrates such as the 2-amino-2-deoxypentoses [75]. In 1982, they reported that the potassium enolate derived from the magnesium salt of the (/ )-atrolactic acid derivative 85 adds to 2,3-0-isopropylidene-D-glyceraldehyde in a highly stereoselective manner giving, after alcohol protection, imine hydrolysis and amine protection, the D-arabinopentoate derivative 86 (Scheme 13.35). Further elaboration leads to 2-acetamido-2-deoxy-D-arabinose 87. In a similar fashion, starting from (5 )-atrolactic acid, 2-acetamido-2-deoxy-D-ribose 88 was prepared [76]. 

Hydroxyacetone 96 is a reagent in an even more remarkable reaction the asymmetric direct three-component Mannich reaction. It is combined with an aromatic amine 98 and the inevitable isobutyraldehyde 89 with proline catalysis to give a very high yield of a compound 99 that might have been made by an asymmetric amino-hydroxylation. The proline enamine of hydroxyacetone, must react with the imine salt formed from the amine and isobutyraldehyde. This is a formidable organisation in the asymmetric step. 

A -Substituted bornyl- and isobornylamines 17-19 are best obtained by reduction of the imines formed from camphor and a suitable amine4, either by isolation of the imine or in situ formation. The substituted amines were used as the lithium salt for enantioselective deprotonation and elimination reactions (Section C ). In almost all cases, the exo-amines (isobornylamines) are formed however, using (S)-l-phenylethylamine as the starting amine, the selectivity is reversed and the enob-amine (bornylamine) is obtained. 

Heterocycles which contain an imine unit (C = N) as part of their ring structure -pyridines, quinolines, isoquinolines, 1,2- and 1,3-azoles, etc. - do not utilise the nitrogen lone pair in their aromatic rr-system (cf. section 1.2) and therefore it is available for donation to electrophiles, just as in any simpler amine. In other words, such heterocycles are basic and will react with protons, or other electrophilic species, at nitrogen, by addition. In many instances the product salts, from such additions, are isolable. 

The aza-Diels-Alder reaction of imines with diene of Danishefsky is an important route to 2,3-dihydro-4-pyridones. A number of Lewis acids have been used to catalyze the reaction in organic solvents. In water the reaction was realized by acid catalysis via iminium salts or by Bronsted acids. The montmorillonite K-10 catalyzed this cycloaddition in water or in aqueous acetonitrile in excellent yield. Recently Kobayashi has performed the reaction in water at room temperature under neutral conditions in two (imine - - diene) or three (aldehyde -b amine -b diene) component versions by using sodium triflate as catalyst. Imine intermediates from the indium-mediated reaction, in aqueous medium at 50° C, between aromatic nitro compounds and 2,3-dihydrofuran undergo aza-Diels-Alder cycloadditions to give tetrahydroquinoline derivatives in good overall yields. ... 

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