Imine formation, double

Fig. 9.27. Condensation of diamines with dicarbonyl compounds (and/or their hydrates) to give N heterocycles. Double imine formation yields quinoxalines (B), double enamine formation leads to dimethylpyrrole (D).

Dicarbonyl compounds and 1,2-diaminoethanes cyclocondense (with double imine formation) to afford 2,3-dihydropyrazines 20 which are conveniently oxidized to pyrazines 21 by CuO or Mn02 in KOH/ethanol ... 

A double imine formation. Such a process may be carried out without catalysis, but mild acid is usually helpful. The mechanism for the first condensation is shown in detail, the second in abbreviated form. 

Formation of pyrazines and quinoxalines has been a focal point of many years of study. The most common method to make these rings relies on the condensation of 1,2-diamines with 1,2-dicarbonyls in ethanol or acetic acid in 35-85% yields. The mechanism proceeds through a double imine formation. Recently improved methods have been reported, employing transition-metal catalysis and microwaves. ... 

Initial imine formation between PMP and cr-keioglutatate is followed by double-bond rearrangement to an isomeric imine and hydrolysis. 

In 2004, Rayner and coworkers reported a dynamic system for stabilizing nucleic acid duplexes by covalently appending small molecules [34]. These experiments started with a system in which 2-amino-2 -deoxyuridine (U-NH ) was site-specifically incorporated into nucleic acid strands via chemical synthesis. In the first example, U-NH was incorporated at the 3 end of the self-complementary U(-NH2)GCGCA DNA. This reactive amine-functionalized uridine was then allowed to undergo imine formation with a series of aldehydes (Ra-Rc), and aldehyde appendages that stabilize the DNA preferentially formed in the dynamic system. Upon equilibration and analysis, it was found that the double-stranded DNA modified with nalidixic aldehyde Rc at both U-NH positions was amplified 34% at the expense of Ra and Rb (Fig. 3.16). The Rc-appended DNA stabilizing modification corresponded to a 33% increase in (melting temperature). Furthermore, imine reduction of the stabilized DNA complex with NaCNBH, resulted in a 57% increase in T. ... 

Figure 3.19 Schematic of the DCC SELEX system. Upper left A library of random 2 -amino RNAs are allowed to equilibrate via imine formation with aldehydes in the presence of target. Bottom left Modified RNAs are bound to the target. Bottom center Modified RNAs bound to the target are separated from unbound RNAs. Bottom right Selected RNAs are eluted and reverse transcribed and amplified to corresponding double-stranded DNA. Upper right The selected double-stranded DNA is transcribed to the 2 -amino RNAs. The selection process is repeated n-cycles and selected conjugated aptamers are identified.

This is one of the finest single-step transformations in the chemical literature. Note that five reactions are achieved in one pot hydrogenation of two double bonds, Cbz deprotection, intramolecular imine formation, and convex-face alkene hydrogenation that establishes the n-Pr stereocenter. 

Because a CO double bond is considerably stronger than a CN double bond, the equilibrium in these reactions often favors the carbonyl compound rather than the imine. In such cases it is necessary to drive the equilibrium to the product. This is usually accomplished by removing the water as it is formed. Some additional examples of imine formation are provided in the following equations ... 

The product is a highly unstable double imine. Aromaticity is immediately restored and a series of proton shifts and C-N bond formation and cleavage give the aromatic indole. In the last diagram the ten-7t-electron indole is outlined in black. 

The second reaction starts with nucleophilic attack by the amine on the more electrophilic carbonyl group - the ketone. Imine formation is followed by cyclization and this second step is i normal nucleophilic substitution at the carbonyl group of an ester (Chapter 12). The imine double bond moves into the ring to secure conjugation with the ester. 

This general aromatic anneiation Finally, the pyridine synthesis is simply a double enamine/imine formation between ammon . sequence came from Hawaii and the two carbonyl groups. Probably the aldehyde reacts first. 

Imine formation and enamine formation appear different because one leads to a product with a C=N double bond and the other leads to a product with a C=C double bond. Actually, though, the reactions are quite similar. Both are typical examples of nucleophilic addition reactions in which water is eliminated from the initially formed tetrahedral intermediate and a new C=Nu double bond is formed. 

The use of TiCl4 did not facilitate the cyclisation and led to the formation of a double imine consuming 2 eq. of fi. Accordingly, primary amines form in the presence of TiCl4 the corresponding imines 8 and the same result is obtained when iminophosphoranes are applied (Scheme 31). 

Imine formation follows the usual pathway (pp. 230-32 of the textbook) but this imine is unstable, as are most primary imines, and it reacts with more benzaldehyde. This reaction starts normally enough but dehydration of the first intermediate produces a strange looking cation with two double bonds to the same nitrogen atom. Addition of another imine gives the final product. The benzene rings play no part in these reactions so we shall represent them as Ph, but they do stablize the final product by conjugation... 

More recently (2004), Joule proposed a novel synthetic route to access the akuammiline scaffold with reports from his group s synthetic efforts toward realizing this plan. Retrosynthetically, they envisioned akuammiline (1) to result from late stage imine formation of ketone 247 (Scheme 32). The functionality at position 16 would then be elaborated from a carbonyl contained in diketone 248, which in turn was planned to be obtained via an intramolecular Claisen condensation and double bond isomerization of enamine 249, the latter the product of an aza-Diels—Alder cycloaddition involving cyclic 1-aza-1,3-diene 250 and an acrylate 251. To access azadiene 250 they planned an oxidative ring opening of bicyclic pyrrole 252. 

Imines are compounds that possess a C=N double bond and are common in biological pathways. Imines are also called Schiff bases, named after Hugo Schiff, a German chemist who first described their formation. A six-step mechanism for imine formation is shown in Mechanism 20.6. It is best to divide the mechanism conceptually into two parts (just as we did to conceptualize the mechanism of acetal formation) (1) The first three steps produce an intermediate called a carbinolamine and (2) the last three steps convert the carbinolamine into an imine ... 

An aldehyde or a ketone reacts with a primary amine to form an imine (sometimes called a Schiff base). An imine is a compound with a carbon-nitrogen double bond. The reaction requires a trace amount of acid. Notice that imine formation replaces a C=0 withaC=NR. 

An aldehyde or a ketone reacts with a secondary amine to form an enamine (pronounced ENE-amine ). An enamine is an o , S-unsaturated tertiary amine—that is, a tertiary amine with a double bond in the a, 8-position relative to the nitrogen. Notice that the double bond is in the part of the molecule that is provided by the aldehyde or ketone, not in the part that is provided by the secondary amine. The name comes from joining ene and amine, with the second e in ene omitted in order to avoid two successive vowels. Eike imine formation, the reaction requires a trace amount of an acid catalyst. 

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