Cyclic Schiff bases

Preparation of spirooxaziridines from cyclic ketones poses no problems nor does oxaziridine synthesis from cyclic Schiff bases, which was preferably carried out with pyrro-lines to give, for example (245) (59JCS2102) and, in connection with tranquilizer synthesis, with heterocyclic seven-membered rings to give, for example, (246) (63JOC2459). 

Additions of aryl- or alkyllithium reagents to N-silylated formamides 508 give the imines 509 in 55-80% yield [90, 91] some of these imines can subsequently be converted into the corresponding //-lactams by reaction with enolates of alkyl butyrates [92]. Conversion of N-silylated butyrolactam 388 into cyclic Schiff bases such as 390, by reaction with methyl- or butyllithium, via O-silylated butyrolactam 389, is discussed in Section 4.8 (Scheme 5.28). 

Figure 5.37 APG can be used to label specifically arginine residues in proteins, producing stable, cyclic Schiff base-like bonds with the side-chain guanidino groups. Photoactivation with UV light then causes ring expansion of the phenyl azide group, initiating covalent bond formation with amines.

The most common cyclization reactions in drug metabolism proceed with elimination of a H20 molecule. These reactions produce lactams, lactones, cyclic Schiff bases, and even more-complex metabolites. 

In this subsection, two types of cyclodehydrations will be discussed, namely the formation of cyclic Schiff bases, and the formation of cyclic enol ethers and cyclic enamines. 

Intramolecular formation of an imino group is possible in compounds that contain properly positioned carbonyl and amino groups (primary or secondary). The equilibrium between the open-chain parent and the cyclic Schiff base product will be pH-dependent, as explained in Sect. 11.6.1. 

The minor metabolite 11.167 in Fig. 11.20 can be viewed as a cyclic Schiff base formed by reaction of the NH2 and C=0 groups. In contrast, the major and unexpected metabolite 11.166 is also a Schiff base, but, more precisely, it is a permanent iminium cation formed between a secondary amino and a keto group. Presumably, formation of 11.166 is facilitated sterically by the spatial proximity of the two reacting groups. Another factor might well be the stability of the iminium cation, which is expected to be high in acidic media (proton repulsion by the positive charge) and in alkaline media (ab-... 

The ancillary N-donor and O-donor ligands are also important in the formation and stabilization of oxomanganese clusters. N-donor ligands are especially common ranging and range from bidentate to predesigned polydentate and include aliphatic, cyclic, Schiff base, and polypyridyl systems (Figures 2 and 3). 

The cyclic Schiff base terimine ligand (161) forms a spin cross-over ternary iron(II) complex [Fe(161)(CN)2]. This has intermediate magnetic behavior, indicating a 50 50 mixture of high-spin... 

Fig. 11.5 Proposed intermediacy of a cyclic Schiff Base (CSB) producing respectively trans- and c/s-PDC through two-step electron transfer and syn-addition of hydrogen atoms at platinum surface.

Reaction of pyruvic acid with H2NNHC(S)NHNH2 gave the cyclic Schiff bases possessing the 1,2,4,5-tetrazepine fragment (Equation 13) <1996MI67>. 

Also in the case of the cyclic Schiff base 76, the bridged bicyclic nature of inter-... 

The earliest reports of constrained Ugi adducts derived from bi-functional precursors appeared in the 1960s with the preparation of penicillin derivatives such as 68, involving sequential Asinger and Ugi four-component reactions (Scheme 11.13). As such, the synthesis represents the shortest preparation of a known penicillin derivative [65], The /Mactam ring is formed after isocyanide addition to the cyclic Schiff base, followed by carboxylate nitrilium ion trapping and acyl transfer to give the final penicillin core. In this example, the amine and carboxylic acid inputs may be considered tethered. 

Further applications for the preparation of jfi-turn mimetics have also been reported by Martens et al. with the synthesis of pipecolic acid derivatives 88 (presumably proceeding via a cyclic Schiff base - not a true post-condensation modification ) [74] and Golebiowski and co-workers who have reported the solid-supported synthesis of bicyclic diketopiperazines with the generic structure 89, via the multi-step synthesis shown in Scheme 11.18 [75]. 

Proline analogs, (2S,4R)-4-methylproline (/ra .s-4-methyl-l-proline) and (2S, 4S)-4-methylproline (ris-4-methyl-l-proline), derive from reduction of their corresponding cyclic Schiff bases (F22) (Fig. 3). 

Another equilibrium partner of the form 102a is the cyclic Schiff base 101a, formed by dehydration. The C=N chromophore in 101a exhibits a weakly positive Cotton effect at 250 nm, by which the proportion of 101a present can be demonstrated. The Cotton effect disappears at pH values below 6. By comparison with 5-amino-5-deoxy-D-xylopyranose (17), 102a is definitely the more stable toward acids. Neither an Amadori rearrangement product, nor aromatization to a p)nTole derivative, is observed down to pH 1.0. 

The use of phenacyl handles 15 is only compatible with the Boc/Bzl strategy since the peptide-resin anchor is not stable to the nucleophilic conditions used in the Fmoc/tBu strategy. Besides the formation of piperazine-2,5-diones, another side reaction can take place on incorporation of the second residue. Attack by the free amino group of the first amino acid on the carbonyl group of the phenacyl resin leads to a cyclic Schiff base.P Both types of side reaction can be minimized using the in situ neutralization protocol. Photolysis is carried out as for nitrobenzyl resins. 

Syntheses of fused quinolizines by annulation of cyclic Schiff bases ([3 + 3] cyclocondensation reactions) 03MI4. 

The second synthesis in this section is a variation on the methodology required to prepare cyclic Schiff bases. However, the product is not a Schiff base per se but a related cyclic tetralactam (14) (Figure 2.5) that forms through the facile, untemplated reaction of ethylenediamine with dimethyl 2,6-pyridinedicarboxylate,... 

The catalyst could be reused several times, an important factor considering the high cost of ruthenium and the ligand. No ruthenium was lost by leaching. Even so, the ruthenium would have to be recovered chemically after the useful life of the catalyst. Chiral ruthenium catalysts can also be used to reduce cyclic Schiff bases in 82 to more than 99% yield with 77-97% ee.82... 

Other cyclization reactions also require a metal cation. For example, the preparation of the following cyclic Schiff base was possible only with a metal ion template (Jackets et al., 1972). Formation of the same ring system but with benzyl substituents rather than methyls also required a template ion. In... 

Curtis and others showed that cyclic condensation also was possible in the absence of a metal template ion, but acid was necessary for those reactions. Possibly, the protonated amines formed an internal hydrogen-bonding network that acted as a template. Cyclization was observed in yields of up to 80% (Curtis and Hay, 1966 Kolinski and Korybut-Daszkiewicz, 1969 Tait and Busch, 1978a, 1978b). The isomers of the formed cyclic Schiff bases were difficult to separate. Reduction of the unsaturated macrocycles gave cyclic polyamines with up to six chiral centers and up to 20 diastereomeric isomers (Hay and Piplani, 1977 Kolinski and Korybut-Daszkiewicz, 1969). 

Template-catalyzed syntheses of peraza-cyclophanes via the cyclic oligo Schiff bases are common (Mandal et al., 1987). The reaction of a dialdehyde and a diamine to form a cyclic oligo Schiff base is usually successful, but only a few of the di or tetra Schiff bases have been reduced to the cyclic amines. Some examples of these cyclic Schiff base-forming reactions have been reported, but this subject will not be reviewed extensively because this book covers the saturated polyaza-crowns and cyclophanes. Reducing the Schiff... 

Synthesis of annelated quinolizine derivatives from cyclic Schiff bases by [2 + 4] cyclocondensation 01MI86. 

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