Hydrolysis of imines and enamines

Hydrolysis of imines and enamines forms aldehydes and ketones. 

In the reduction of imines and enamines with hydrogen telluride and sodium hydrogen telluride, hydrolysis leading to primary amines and carbonyl compounds is frequently competitive with the reduction. This undesired side reaction is minimized by the addition of triethylamine, in the case of hydrogen telluride. ... 

Because imines and enamines are formed by a set of reversible reactions, both can be converted back to carbonyl compounds by hydrolysis with mild acid. The mechanism of these reactions is exactly the reverse of the mechanism written for the formation of imines and enamines. In the hydrolysis of enamines, the carbonyl carbon in the product comes from the hybridized carbon bonded to the N atom in the starting material. 

Ojima and colleagues found that enamine (imine) 9 from aldehyde 8 readily cycUzed to indoles 10 upon treatment with LDA (equation 5) [5, 6]. The A-allyl group in 10 was removed by rhodium trichloride isomerization followed by acidic hydrolysis of the A-enamine (97% yield). Along similar lines. Filler s team reported an improved synthesis of 4,5,6,7-tetrafluoroindole 13 (equation 6) [7] over the method they had reported earlier. The improvements are in the reduction of nitrile 11 to phenethylamine 12 and the final oxidation to 4,5,6,7-tetrafluoromdole (13). 

Hydrolysis of acetals, imines, and enamines under acidic conditions produces ketones or aldehydes. 

Reaction of 10 with 4-pentenyllithium gave 11. Enolization of 10 competed with imine addition and thus, recycling of this material was needed to achieve a respectable overall yield of 11 from ketone 9. Acid hydrolysis of 11 furnished enamine 12 after neutralization. An acid-mediated Mannich reaction converted 12 to a mixture of epimeric ketones 13. Oxidation of the 27-methyl group provided formamide 14. 

The transaldolase functions primarily to make a useful glycolytic substrate from the sedoheptulose-7-phosphate produced by the first transketolase reaction. This reaction (Figure 23.35) is quite similar to the aldolase reaction of glycolysis, involving formation of a Schiff base intermediate between the sedohep-tulose-7-phosphate and an active-site lysine residue (Figure 23.36). Elimination of the erythrose-4-phosphate product leaves an enamine of dihydroxyacetone, which remains stable at the active site (without imine hydrolysis) until the other substrate comes into position. Attack of the enamine carbanion at the carbonyl carbon of glyceraldehyde-3-phosphate is followed by hydrolysis of the Schiff base (imine) to yield the product fructose-6-phosphate. 

Many acids other than sulfuric acid have been used for the challenging cyclodehydration step. It is important to note that when the concentration of sulfuric acid is below 70%, hydrolysis of the imine or enamine occurs. As previously mentioned, HCl/AcOH, ZnCla, PPA, POCI3, and lactic acid have been successfully applied to promote the cyclization. Chloroacetic acid was found to perform similar to lactic acid. Concentrated HCl, p-TsOH, and have proven beneficial in generating linear... 

The Michael additions of chiral cycloalkanone imines or enamines, derived from (FV l-l-phcnyl-ethanamine or (5)-2-(methoxymethyl)pyrrolidine, are highly diastereofacially selective reactions providing excellent routes to 2-substituted cycloalkanones. This is illustrated by the addition of the enamine of (S)-2-(methoxymethyl)pyrrolidine and cyclohexanone to 2-(aryl-methylene)-l,3-propanedioates to give, after hydrolysis, the (2 5,a.S )-oxodicstcrs in 35-76% yield with d.r. (2 S,aS)/(2 S,a/ ) 94 6- > 97 3 and 80-95% ee214. 

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. 

Scheme 6.104 Key intermediates of the proposed catalytic cycle for the 100-catalyzed Michael addition of a,a-disubstituted aldehydes to aliphatic and aromatic nitroalkenes Formation of imine (A) and F-enamine (B), double hydrogen-bonding activation of the nitroalkene and nucleophilic enamine attack (C), zwitterionic structure (D), product-forming proton transfer, and hydrolysis.

A simple preparation of electron-poor 2-azadienes and the preliminary study of their ability to participate in [4 + 2] cycloadditions was done almost simultaneously by out group (87CC1195) (Scheme 49). The preparation of 2-azadienes 212 with two appended methoxycarbonyl groups was achieved, in a multigram scale and in nearly quantitative yield, by the insertion reaction of N- trimethylsilyl imines 210 into the carbon—carbon triple bond of dimethyl acetylenedicarboxylate to give 211 followed by protodesilylation with CsF/MeOH. Azadienes 212 underwent at room temperature inverse-electron demand [4 + 2] cycloaddition with cyclic enamines to give exclusively exo-cycloadducts 213 in 82-95% yield. Acid hydrolysis of them resulted in their aromatization to yield 2-pyrindine (n = 1] and isoquinoline (n = 2) derivatives 214. 

The intermediacy of an imine was postulated. In order to test this hypothesis and to find an explanation to the introduction of one silyl group on the para-position on the ring, this reaction has been revisited. Avoiding hydrolysis of the reaction medium, the real reaction product was identified as being an enamine, the likely precursor of the ASMA.180... 

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