Amines form enamines

The mechanisms illustrate why the reaction of 1° amines with carbonyl compounds forms imines, but the reaction with 2° amines forms enamines. In Figure 21.10, the last step of both mechanisms is compared using cyclohexanone as starting material. The position of the double bond depends on which proton is removed in the last step. Removal of an N—H proton forms a C=N, whereas removal of a C-H proton forms a C=C. 

A completely different, important type of synthesis, which was developed more recently, takes advantage of the electrophilicity of nitrogen-containing 1,3-dipolar compounds rather than the nucleophilicity of amines or enamines. Such compounds add to multiple bonds, e.g. C—C, C C, C—O, in a [2 + 3 -cycioaddition to form five-membered heterocycles. 

Primary amines undergo nucleo philic addition to the carbonyl group of aldehydes and ketones to form carbinol amines These carbinolamines dehydrate under the conditions of their formation to give N substituted imines Secondary amines yield enamines... 

Experiments designed to clarify the situation were carried out by Wittig and Mayer (40). It was shown that changing the molar ratio of amine (diethylamine, di- -butylamine, or diisobutylamine) to -butyraldehyde from 1 1 to 2 1 did not affect the yield of enamine (53- 64%, based on the aldehyde). Contrariwise, changing the ratio of amine (morpholine, piperidine, or pyrrolidine) to n-butyraldehyde from 1 1 to 2 1 boosted the yields from 52-57 % to 80-85 %. The authors interpret these data as indicating that the cyclic amines form aminals with n-butyraldehyde, while the open-chain do not. Infrared evidence is stated as having shown that the aminal originates not from attack of excess amine on the enamine, which is stable under the conditions of the reaction, but from the N-hemiacetal (17). 

Primary amines add to aldehydes and ketones to form imines, R-N=CR2-Secondciry cimines react to form enamines, R 2C=CR(NR2). Hydroxylamine reacts to form an oxime, R2C=NOH. Hydrazine reacts to form a hydrazone,... 

Secondary amines do not generally form enamines with 2-acetyldimedone, and this protective group can therefore be used for the selective protection of primary amines in the presence of secondary amines [234,309], Support-bound 2-acetyldimedone has also been used as a linker for amines [312] (see Section 3.6). 

The same authors have also reported the synthesis of 2-amino quinolines46, Scheme 5.28. Secondary amines were reacted with aldehydes to form enamines subsequent addition of 2-azidobenzophenones initially forms triazoline intermediates, which undergo a thermal rearrangement and intermolecular base-catalysed cyclocondensation to produce 2-amino quinolines. The reactions were run at 180°C for 10 min (the time includes 3 min required for enamine formation) to give the products in 57-100% yields. 

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

Scheme 2.1 The enamine catalytic cycle. An enamine derived from an amine- or amino acid-catalyst can react with a variety of electrophiles. The aldehyde and ketone reactants that form enamines and act as nucleophiles are often described as donors . Aldehyde and imine reactants that serve as electrophiles are described as acceptors for aldol and Mannich reactions, respectively. Ketones also serve as acceptors for aldol reactions.

Secondary amines react with ketones that contain an H atom in the a-position through an addition and subsequent El elimination to form enamines (Figure 9.29). In order for enamines to be formed at all in the way indicated, one must add an acid catalyst. In order for them to be formed completely, the released water must be removed (e.g. azeotropically). The method of choice for preparing enamines is therefore to heat a solution of the carbonyl compound, the amine, and a catalytic amount of toluenesulfonic acid in cyclohexane to reflux in an apparatus connected to a Dean-Stark trap. Did someone say Le Chateher ... 

Secondary amines react with carbonyl compounds to form enamines ... 

Tertiary amines form complexes with mercury(II) ion, which then give iminium ions by loss of a piotoa Addition of perchloric acid permits isolation of the iminium ion as the perchlorate salt and generally the more-substituted ion is favored (equation 14). Intramolecular trapping by a hydroxyalkyl group is also possible to form aminals (equation 15). The lactam products result from over-oxidation, which is promoted by heat. Basification on the other hand usually allows the isolation of enamines although hydroxyenamines have been obtained by reaction of enamines with mercury(II) acetate (equation 16), while dihydroaromatic systems undergo aromatization (equation 17). ... 

Carbonyl often exists as gem-diol (hydrate) in a aqueous solution (R— CO—R + H2O. R—C(0H)2—R ). The nucleophile (hydroxide ion, HO—) in a base-catalyzed reaction is much more powerful than a water molecule, the nucleophile in neutral media. Aldehydes react faster than ketones because equilibrium constants for hydration are more favorable for aldehydes than they are for ketones. Aldehydes [CO(R )(H)] also react readily with amines (primary amines form an imine or Schiff bases R—N=C(R )(H) -1- H2O while secondary amines form an enamine (must have an aldehyde with hydrogen on alpha carbon). 

Secondary amines react with aldehydes and ketones to form enamines. Enamines are also susceptible to acid-catalyzed hydrolysis. 

Aldehydes and ketones react with 1° amines to form imines and with 2° amines to form enamines. Both reactions involve nucleophilic addition of the amine to the carbonyl group to form a carbinolamine, which then loses water to form the final product. 

In contrast to ammonia, primary, secondary, and tertiary amines can add to aldehydes and ketones to give different kinds of products. Primary amines give imi-nes and secondary amines gives enamines (10-69). This section will focus on imines. Reduction of co-azido ketones leads to the amino-ketones, which cyclizes to form a 2-substituted pyrroline. Reduction of nitro-ketones in the presence... 

A new acyl anion equivalent derived from an aldehyde, a secondary amine and diphenylalkylphos-phine oxide, e.g. (N-morpholinomethyl)diphenylphosphine oxide, reacts with aldehydes or ketones to form enamines, which on acid hydrolysis afford aldehydes or ketones (Scheme 32). The usefulness of this acyl anion equivalent is demonstrated by the synthesis of dihydrojasmone and (Z)-6-henicosen-11-one. ... 

This reaction forms the required pyrrole in one step First, the oxime is reduced to an amine then the amino group forms an imine with the most reactive carbonyl group (the ketone) in the keto-diester. Finally, the very easily formed enamine cyclizes on to the other ketone. 

Amines and -keto carbonyl compounds form enamines in high yields. This reaction has been used to protect amino acids and amino acid esters (Scheme 17). Enamines (28) from acyclic P-dicarbonyl com-... 

Alternatively, the C-H bond next to the carbocation can be deprotonated (path Dg). This is common for secondary amine sources (NuH is R2NH), in acidic media, with removal of water to form enamines. 

Aldehydes and ketones react with primary amines (RNH2) to yield imines and react with secondary amines (R2NH) to form enamines. 

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