Amines imine formation from

In a study of imine formation from aldehydes in aqueous solution, formation constants have been correlated with three parameters the pK.d and HOMO energy of the amine and the LUMO energy of the aldehyde.23... 

In Ugi s four-component condensation, imine formation from an aldehyde 1 and an amine 2 is likewise the initiating step [5, 6] a carboxylic acid 9 and an isonitrile 10 are the other reaction components, which finally yield the bisamide 11. Both for this reaction and the Strecker synthesis, the galactosylamine 12 is particularly suitable for carrying out a stereoselective reaction (synthesis of 13) [4d-e, 5f. With an aminoglucopyranose as a chiral auxiliary, the stereoselectivity of the reaction can be further increased [5b]. Amino acids as condensation components yield particularly impressive results. For instance, the imino-... 

Three-component reactions of aldehydes, amines, and allyltributyltin also proceeded smoothly in micellar systems with Sc(OTf)3 as Lewis acid catalyst, to afford the corresponding homoallylic amines in high yields (Eq. 19) [68]. Not only aromatic aldehydes but also aliphatic, unsaturated, and heterocyclic aldehydes worked well. The procedure is very simple—merely mixing an aldehyde, an amine, and allyltributyltin in the presence of Sc(OTf)3 and SDS in water no homoallylic alcohol (an adduct between an aldehyde and allyltributyltin) was produced. It was suggested that imine formation from aldehydes and amines was very fast under these conditions, and that the selective activation of imines rather than aldehydes was achieved. 

Imine formation from such reagents as hydroxyl amine, and 2,4-dinitro-phenylhydrazine are useful because the products of these reactions— oximes and 2,4-dinitrophenylhydrazones (2,4-DNP s), respectively— are often crystalline and easy to handle. Such crystalline derivatives are sometimes prepared as a means of purifying and characterizing liquid ketones or aldehydes. 

Nucleophilic reactions. Chiral epoxides are converted into 2,2-dimethyl-l,3-dioxolanes with inversion of configuration by reaction with acetone. An efficient procedure for imine formation from ketones and amines specifies TiCU as promoter. Hydrolysis (or alcoholysis) of RCONH2 is achieved in the presence of TiCU in acidic media. 

These derivatives are called oximes, hydrazones, phenylhydrazones, and 2,4-dinitro-phenylhydrazones, respectively. The mechanisms by which these C = N derivatives form are similar to the mechanism for imine formation from a primary amine. As with imines, the formation of ( ) and (Z) isomers is possible. 

Imine Formation from Amines and Aldehydes or Ketones... 

Processes such as imine formation from a primary amine and an aldehyde or ketone, in which two molecules are joined with the elimination of water (or other small molecules such as alcohols), are called condensations. 

Another type of bifunctional catalysis has been noted with a,cn-diamines in which one of the amino groups is primary and the other tertiary. These substituted diamines are from several times to as much as 100 times more reactive toward imine formation than similar monofunctional amines. This is attributed to a catalytic intramolecular proton transfer. 

Reaction of an aldehyde or ketone with a secondary amine, R2NH, rather than a primary amine yields an enamine. The process is identical to imine formation up to the iminium ion stage, but at this point there is no proton on nitrogen that can be lost to form a neutral imine product. Instead, a proton is lost from the neighboring carbon (the a carbon), yielding an enamine (Figure 19.10). 

Amines can react with various carbonyl compounds and their derivatives in aqueous media to give the corresponding imine derivatives. These reactions have been discussed in related chapters. The synthetically most useful reaction of this type is the formation of imines and imine derivatives from the condensation of amines with aldehydes and ketones. Water is an excellent solvent for such condensation reactions. For example, water was found to be an ideal solvent for a high-yield, fast preparation of easily hydrolyzable 2-pyrrolecarbaldimines.23 In the presence of Cu2+, the reaction afforded the corresponding Cu(II) chelates (Eq. 11.19). 

TiCl4 also effectively promotes formation of imines and enamines from carbonyl compounds (Scheme 31). The combination of imine formation using TiCl4 and reduction leads to reductive alkylation of an amine moiety.113,114... 

Reaction of A,A-dimcthylsullamoyl aziridines 323 and 325 with primary amines furnishes substituted 1,2,5-thiadiazolidine 1,1-dioxides 324 and 326, respectively, in a regioselective manner <06SL833>. Aziridine 325 is made from ( I /t,6,S ,Z)-bicyclo[4.2. l]non-3-en-9-one in two steps /V,/V-dimethylsulfamoyl imine formation using dimethylsulfamide and subsequent reaction with trimethylsulfoxonium ylide. The product from the reaction with 4-methoxy-benzyl amine can be subsequently manipulated (debenzylation and derivatization) to give the alternative nitrogen substitution pattern in a controlled manner. 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

The lactam formation from the oxidation of cyclic amines (353, for example) probably proceeds via intermediate 364. The nitrogen-iodine bond dissociates to give imine 365, which reacts again with a second equivalent of iodosobenzene to give another intermediate 366. Finally, 366 on reductive... 

The aldehyde can be replaced by an imine and the reaction is then called the aza-Baylis-Hillman reaction [87, 88]. (3-Amino-a-methylene structures obtained in this way could further be converted to a range of biologically important molecules, such as p-amino acids [89]. First reaction of this kind was published in 1984 [90]. Tosylimines and ethylacrylate reacted in the presence of DABCO as catalyst to give p-aminoesters. First three-component aza-Baylis-Hillman reaction was published in 1989 by Bertenshaw and Kahn [91], with imine formation in situ from an aldehyde and an amine. In the presence of triphenylphosphine as catalyst, the reaction with methylacrylate led to the formation of the p-amino-ot-methylene esters and ketones in good yields (Scheme 38). 

Using the optimized system for the two-component reaction, the same group [89] tested the three-component reaction, starting from an aldehyde, an amine and a phosphite (Scheme 42). An orthoester (trialkyl orthoformate, methyl or ethyl) was added to remove the formed water and to promote the imine formation, which was beneficial for the reaction however, these trials afforded maximally 49% yield due to the low conversions and low selectivities towards the desired aminophosphonates. 

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