Secondary enamines hydrolysis

Normally the less substituted double-bond isomer (la) is the more reactive since reaction at the more substituted position It engenders severe allylic interactions (A1,3-strain5) in the transition state. Further reaction therefore occurs preferentially to give the / ,/ -disubstituted enamine or iminium salt (3) and hence the a,a -disubstituted ketone (5) on hydrolysis. However, there are exceptions to this (see Sections III.B, V and VI.D). A recent development uses the observation6 that such steric interactions do not apply to secondary enamines (Section VIII) since a conformation (2) can be adopted... 

Recently, Capon and Wu49 have reported the generation of secondary enamines from their TV-trimethylsilyl derivatives through hydrolysis. In DMSO-d6 (99% v/v)-D20 (1% v/v) solution, enamine 40 is converted to the TV-deuteriated enamine 41 quantitatively in 5-10 min at room temperature. The solution obtained is stable for several hours, but over a period of 2-3 days 41 is oxidized to acetone and iV-deuterio-TV-phenylforma-mide. On adding 15% (v/v) D20/DC1 (0.1 M) to the solution, enamine 41 is completely hydrolyzed to 2-[2//]isobutyraldehyde and aniline without detection of any intermediates. Enamine 42 is formed by the acid-catalyzed hydrolysis of 40 (Scheme 3). Similar results are obtained with other iV-aryl enamines. 

The carboethoxy stabilized secondary enamines, 25 and 26, were studied by Guthrie and Jordan68. In the absence of buffer, and at pH 5 to 6, acid catalysis is evident and a solvent kinetic isotope effect, (kH+/kD+) = 2.3, is found for 25. These results clearly support rate-controlling C-protonation of the enamine the catalytic constants are included in Table 9. Both 25 and 26 show general-acid catalysis of hydrolysis in the pH... 

Capon and Wu have shown that the rate of hydrolysis of secondary enamines of cyclohexanone (13 and 14) is decreased only slightly by the 2) methyl group. They have therefore concluded that the methyl substituent has little effect on the ground state or the transition state conformations of secondary enamines . However, in this case there is no developing allylic strain whether the transition state is reactant-like or product-like (see also Section VIII) and pn-conjugation is uninhibited. The pn-conjuga-tion in secondary, -disubstituted acyclic enamines (15) compared to the corresponding tertiary enamines (16) is also demonstrated by the UV and NMR evidence provided by Capon and Wu . 

Secondary amines react smoothly with 3-ketones to give enamines and good selectivity is achieved in the presence of 7-, 12-, 17- and 20-ketones. With pyrrolidine the reaction takes place under very mild conditions and no catalyst is usually required. Hydrolysis occurs by simply heating in ethanol. 

Recently Stamhuis et al. (33) have determined the base strengths of morpholine, piperidine, and pyrrolidine enamines of isobutyraldehyde in aqueous solutions by kinetic, potentiometric, and spectroscopic methods at 25° and found that these enamines are 200-1000 times weaker bases than the secondary amines from which they are formed and 30-200 times less basic than the corresponding saturated tertiary enamines. The baseweakening effect has been attributed to the electron-withdrawing inductive effect of the double bond and the overlap of the electron pair on the nitrogen atom with the tt electrons of the double bond. It was pointed out that the kinetic protonation in the hydrolysis of these enamines occurs at the nitrogen atom, whereas the protonation under thermodynamic control takes place at the -carbon atom, which is, however, dependent upon the pH of the solution (84,85). The measurement of base strengths of enamines in chloroform solution show that they are 10-30 times weaker bases than the secondary amines from which they are derived (4,86). 

The next seven references are cited not because of the experimental procedures described but because they indicate diversification in the types of enamines prepared and studied. Both Paquette (25) and Kasper 26) have condensed 2,5-methylene-l,2,5,6-tetrahydrobenzaldehyde (5-nor-bornene-2-carboxyaldehyde) (2) with several cyclic and open-chain aliphatic secondary amines. Kasper studied the ratio of endo to exo aldehyde formed upon hydrolysis of these enamines and the dihydro enamines. Paquette investigated the addition of sulfene to the enamines. -Fluoro-... 

Hydrolysis of simple enamines appears to be very easy and decomposition to the corresponding carbonyl compound and the secondary amine can be achieved readily by adding water to these compounds. Basicity as well as... 

Hydrolysis of an enamine yields a carbonyl compound and a secondary amine. Only a few rate constants are mentioned in the literature. The rate of hydrolysis of l-(jS-styryl)piperidine and l-(l-hexenyl)piperidine have been determined in 95% ethanol at 20°C 13). The values for the first-order rate constants are 4 x 10 sec and approximately 10 sec , respectively. Apart from steric effects the difference in rate may be interpreted in terms of resonance stabilization by the phenyl group on the vinyl amine structure, thus lowering the nucleophilic reactivity of the /3-carbon atom of that enamine. 

The differenee in reaction rates of the amino alcohols to isobutyraldehyde and the secondary amine in strong acidic solutions is determined by the reactivity as well as the concentration of the intermediate zwitterions [Fig. 2, Eq. (10)]. Since several of the equilibrium constants of the foregoing reactions are unknown, an estimate of the relative concentrations of these dipolar species is difficult. As far as the reactivity is concerned, the rate of decomposition is expected to be higher, according as the basicity of the secondary amines is lower, since the necessary driving force to expel the amine will increase with increasing basicity of the secondary amine. The kinetics and mechanism of the hydrolysis of enamines demonstrate that not only resonance in the starting material is an important factor [e.g., if... 

Alternatively, cyclohexanone may initially be transformed into an enamine with a secondary amine, here pyrrolidine. This intermediate enamine can act as a nucleophile and can be alkylated at the P-position using methyl iodide. Finally, 2-methylcyclohexanone may be generated by hydrolysis of the iminium system, effectively a reversal of enamine formation. This gives us two routes to 2-methylcyclohexanone, a short process using the very strong base LDA and... 

This is a general method of preparing enamines from a secondary aliphatic amine and cyclohexanone or cyclopentanone. Acylation of such enamines is the first step in a general procedure for increasing the chain length of a carboxylic acid by 5 or 6 carbon atoms and of a dicarboxylic acid by 10 or 12 carbon atoms.6 Alkylation of enamines of cyclohexanones by alkyl halides 7 or electrophilic olefins,8 followed by hydrolysis, is a good route to a-monoalkyl cyclohexanones. 

Copper(I) salts of enamines have been allylated with the 2-allyloxybenzimidazoles to give y,5-unsaturated ketones upon hydrolysis (79CL957). Primary allylic ethers react preferentially at their a-carbon with retention of double bond configuration whereas secondary allylic ethers react mainly at the y-carbon to afford alkenes of predominantly (E)-stereochemistry. 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

In streptocyanine dyes both ends of the methine chain are joined directly to nitrogen atoms, and a double enamine structure is thus present. The dyes are extremely susceptible to hydrolysis, particularly if they contain secondary nitrogen atoms. Stable dyes are obtained if the nitrogen is part of a heterocyclic ring system. Streptocyanine dyes are brilliant yellow dyes that dye polyacrylonitrile and acid-modified polyamide fibers with outstanding lightfastness [1],... 

The direct activation and transformation of a C-H bond adjacent to a carbonyl group into a C-Het bond can take place via a variety of mechanisms, depending on the organocatalyst applied. When secondary amines are used as the catalyst, the first step is the formation of an enamine intermediate, as presented in the mechanism as outlined in Scheme 2.25. The enamine is formed by reaction of the carbonyl compound with the amine, leading to an iminium intermediate, which is then converted to the enamine intermediate by cleavage of the C-H bond. This enamine has a nucleophilic carbon atom which reacts with the electrophilic heteroatom, leading to formation of the new C-Het bond. The optically active product and the chiral amine are released after hydrolysis. 

If a proton is added to enamine, diastereomers are possible products when an optically active secondary amine is used, assuming the iminium salt has been produced. To investigate this matter, the series of reactions shown in Figure 4 is performed. The salt is made from the acid using HC1, and D20 hydrolysis of the resultant salt is carried out. Since deuterium is not incorporated into the recovered a-phenylpropionaldehyde, chirality is believed to be induced before the hydrolysis (4). 

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