Iminazoline

Asymmetric Transformation of a-Substituted Carbonyl Compounds Via Enamine or Iminazoline Formation... 

The secondary amines of a five-membered ring and six-membered ring are used as the amine component. Since 2-methylpiperidine is chiral, this piperidine is believed to form diastereomeric iminium salts with chiral carbonyl compounds. (See section entitled Asymmetric Transformation via Iminazoline Formation, for further discussion.)... 

A comparison of enamine and iminazoline structures is shown in Figure 10. There are two types of structural isomerism in the proton-added type of enamine. Differences between the enamine and iminazoline arise because the former is stabilized as the enamine type, whereas the latter is stabilized as the imine type. 

In Table V, the yields of hydrolysis and optical purity of amino acids that are recovered from iminazoline are shown. These imin-azolines are isolated from the reaction mixture of the scheme shown in Figure 11. 

Differences were observed with the types of diamine used. In the case of aminomethylpyrrolidine, iminazoline yield is 86%, from which approximately 90% alanine is recovered its optical purity is approximately 93% R-enantiomeric excess regardless of whether S-alanine or R-alanine is the starting material. Thus, we are confident that the alanine has been transformed asymmetrically (10). 

On the other hand, in the case of isopropylpropylene diamine, the configuration of the recovered alanine is retained. Also, the hydrolysis is difficult and the iminazoline yield is very low. 

To ascertain the presence of asymmetric transformation, mutarota-tion in solution was determined. Figure 12 shows the mutarotation of the above products of alanyl iminazolines in methanol solution. 

For these reactions to occur, we believe that an iminazoline ring and an a-branched carbon must be coplanar. A reaction sequence is depicted in Figure 14. An environment conductive to asymmetric transformation is required. 

Figure 14. Mutarotation of an iminazoline (a) removal from the system by crystallization (b) asymmetric transformation, but no preferential crystallization (c) racemization and (d) no epimerization...

The optical purity of the iminazoline consisting of alanine and 2-aminopiperidine can be increased to 93.8 (e.e.)% by crystallizing it In Figure 14(a), once a crystal is removed to the outside of the system, it forms the solution in which asymmetric transformation is carried out the second-order asymmetric transformation where further transformation develops is obtained. In the case of crystallization of a dia-stereomer, 100 (e.e.)% might be possible. In this instance, the alanine appears to be racemized when the iminazoline ring is decomposed with strong acid. 

In Figure 14(b), the combination of proline and 2-aminomethyl pyrrolidine, the asymmetric transformation was observed but no preferential crystallization occurred. In Figure 14(c) only racemization was observed. Moreover, in Figure 14(d), non-coplanarity of the iminazoline and a-branched carbon prevented the double-bond shift and epimerization did not occur. 

In the mutarotation experiment of iminazoline from alanine and isopropylpropylenediamine, the recovered alanine residue racemized entirely in methanol solution. Why, then, can the iminazoline containing the optically retained amino acid residue be synthesized ... 

Table VI. Results of Mutarotation Experiments Using an Amino Acid and an Iminazoline...

In both instances, the mutarotation velocity with pyrrolidine was faster than with the other amines. When iminazoline synthesis was conducted between alanyliminoether and 2-aminomethylpyrrolidine, excess pyrrolidine in the reaction media probably accelerated the epimerization reaction. Racemization is faster than crystallization of this, diastereomer, which is less soluble than the other diastereomers. In the case of isopropylpropylenediamine, the excess amine racemizes poorly, so the crystallization was faster than the racemization. 

Tolazoline. 4,5-Dihydro.2.(phenyimethyl)-IH. imidazole 2-benzyl-2-imidazotine 2-benzyl-2-iminazoline benzazoline 2-benzyl-4,5 -imidazoline phenylmethylimid-azoline Priscoltne Priscol Vasodil Prefaxil Benzidazol ... 

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