Amine-imine equilibrium

The apparent, very substantial shift of the amine-imine equilibrium toward the imine form in 5,6-dihydrocytosine (22) with respect to cytosine... 

It should be noted that the keto-enamine tautomers of Schiff bases are observed always when the latter are derived from 2-hydroxynaphthaldehyde and aniline. However, in Schiff bases derived from salicylaldehyde and aniline, the new band at >400 nm in UV-Vis spectra was not observed in both polar and non-polar solvents, but it appeared in acidic media. In this workl which contains a quite good survey of the investigations of tautomerism in Schiff bases, the effects of the solvent polarity and acidic media on the phenol-imine keto-amine tautomeric equilibrium in systems 55 and 56 were reported. It was shown by H NMR and UV-Vis spectra that compound 55 is in tautomeric equilibrium of structures 55a and 55b in both polar and non-polar solvents (equation 17), whereas the tautomer 56b was not observed for compound 56 (equation 18) . ... 

A generalized pathway for imine-forming reactions is shown Scheme 1. The protonated amine in equilibrium with the protonated imine (A imh ) must first ionize to form unprotonated amine (K ) in order for the reaction to occur. The unprotonated amine adds (reversibly at high pH) to form the zwitterionic intermediate k ) which undergoes proton transfer to become the neutral... 

Fig. 1. Typical equilibrium concentrations of ketone, amine, imine and iminium ion (see text).

A generalized pathway for imine-forming reactions is shown Scheme 1. The protonated amine in equilibrium with the protonated imine must first... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

Polar C=Y double bonds (Y = NR, O, S) with electrophilic carbon have been added to suifinic acids under formation of sulfones. As in the preceding section one must distinguish between carbonyl groups and their derivatives on the one hand, and carboxylic acids (possessing leaving groups at the electrophilic carbon) on the other. Aldehydes " of sufficient reactivity—especially mono-substituted glyoxals - —and their aryl or arylsulfonyl imines have been added to suifinic acids (in a reversible equilibrium) to yield a-hydroxy or a-amino sulfones the latter could also be obtained from the former in the presence of primary amines (equation 26). 

The nitrogen analogs of ketones and aldehydes are called imines, azomethines, or Schiff bases, but imine is the preferred name and we use it here. These compounds can be prepared by condensation of primary amines with ketones or aldehydes.102 The equilibrium constants are unfavorable, so the reaction is usually driven forward by removal of water. 

Imines and iminium ions are nitrogen analogs of carbonyl compounds and they undergo nucleophilic additions like those involved in aldol reactions. The reactivity order is C=NR < C=0 < [C=NR2]+ < [C=OH]+. Because iminium ions are more reactive than imines, the reactions are frequently run under mildly acidic conditions. Under some circumstances, the iminium ion can be the reactive species, even though it is a minor constituent in equilibrium with the amine, carbonyl compound, and unprotonated imine. 

Similarly, imines can be formed by the condensation of ketones and suitable primary amines under microwave conditions (Scheme 6.148). Since the formation of imines is an equilibrium process, these transformations are best carried out under... 

The TEAF system can be used to reduce ketones, certain alkenes and imines. With regard to the latter substrate, during our studies it was realized that 5 2 TEAF in some solvents was sufficiently acidic to protonate the imine (p K, ca. 6 in water). Iminium salts are much more reactive than imines due to inductive effects (cf. the Stacker reaction), and it was thus considered likely that an iminium salt was being reduced to an ammonium salt [54]. This explains why imines are not reduced in the IPA system which is neutral, and not acidic. When an iminium salt was pre-prepared by mixing equal amounts of an imine and acid, and used in the IPA system, the iminium was reduced, albeit with lower rate and moderate enantioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Nevertheless, as other kinetic studies have indicated a pre-equilibrium with imine, it is possible that the proton formally sits on the catalyst and the iminium is formed during the catalytic cycle. It is, of course, possible that the mechanism of imine transfer hydrogenation is different to that of ketone reduction, and a metal-coordinated imine may be involved [55]. 

The threading-followed-by-capping method has been recently employed by Stoddart to prepare a [2]rotaxane under thermodynamic control [60]. In this approach, the dibenzylammonium ion 28 - which is terminated by an aldehyde function - is mixed with the dibenzo[24]crown-8 ether (20) to form a threaded species. Upon addition of a bulky amine, the aldehyde-terminated template can be converted into an imine in a reversible reaction establishing a dynamic equilibrium (see 29 and 30 in Scheme 17). 

Phosphorylated allenes 195 (R1 = H or Me) are a source of secondary ( )-allylamines. The allenes are treated with an amine R2NH2 (R2 = t-Bu or 4-MeCgH4 and the products, which exist as equilibrium mixtures of enamines 196 and imines 197, are olefinated by successive reaction with methyllithium and an aldehyde R3CHO (R = i-Bu, 4-MeCgH4, PhCH2CH2 etc). Reduction with sodium borohydride finally yields the... 

In the presence of excess monoalkylamine, carbonyl compounds in aqueous solution are in equilibrium with the corresponding imine. In most cases these imines cannot be isolated but they are reduced at a less negative potential than the carbonyl compound. Selective reduction of such equilibrium mixtures is a useful route to alkylamines from ketones in yields of 70-90%. The process fails with hindered ketones such as camphor and with bulky amines such as fert.-butyl amine. Overall the reaction has advantages of lower costs and simpler work-up compared to the use of cyanoborohydride reducing agents. In the electrochemical reaction, protonation of carbanion intermediates occurs from the more hindered side and where two isomeric products are fomied, the least hindered amine predominates [193]. 

Inspired by a bright report from Katritzky and coworkers on the use in Reformatsky reactions of a variety of benzotriazolyl aminals121, which in solution are in equilibrium with the corresponding imines, the formaldehyde aminal 61122 was reacted with lc, Zn and TMSC1 to give adducts 62 (equation 39), which can be successively converted into /3-lactams upon treatment with f-BuMgCl. 

The product of this last reaction is an imine, containing a C-N double bond. The formation of these compounds is an equilibrium and they are very easily hydrolysed. More stable imines are formed from hydroxyl-amine HONH2. Write down the complete reaction between this compound and PhCO.Me (using the N atom as nucleophile). 

However Morita and Nagakura104 concluded from similar studies that in aqueous solution cytosine exists as an equilibrium mixture of two forms, 2 and 6, only. According to these authors the first form predominates in trimethyl phosphate and water at room temperature, but the second prevails at high temperature. The imine form is considered to predominate also in acetonitrile. From the temperature dependence of the absorption spectrum of cytosine in aqueous solution, Morita and Nagakura estimated the tautomeric ratios Kf-e to be equal to 33, 14, and 8 at 30, 50, and 70°, respectively. The energy115 and entropy differences between the imine form 6 and the amine form 2 were evaluated as 5.5 kcal/mole and 12 cal/mole. deg., respectively. 

As we see, the contribution of the imine forms of N4-substituted cytosines to the tautomeric equilibrium becomes more important with respect to the amine forms with increase of the electronegativity of the N4-substituent in the series H, NH2, OH(OMe). 

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