Schiffbase reaction

Schiffbase, 1147 Scurvy vitamin C and, 772 sec-Butyl group, 84 Second-order reaction, 363 Secondary alcohol, 600 Secondary amine, 917 Secondary carbon, 84 Secondary hydrogen. 85 Secondary structure (protein), 1038-1039... 

Formation of /1-lactams by the reaction of an acid chloride, a SchifFbase and a tertiary amine (Eq. 62) appears to involve multiple pathways, some of which are very fast at higher temperatures. When conducted in open vessels in unmodified micro-wave ovens, high level irradiation leads to preferential formation of the trans -lactams (55%) whereas, at low power, the cis isomer was obtained as the only product (84%). The failure of the cis isomer to isomerize to the trans compounds is an example of induced selectivity. 

Scheme 4.29 Reaction of the acid chloride of tetrachlorophthaloyl glycine with a Schiffbase.

Here the hapten (Scheme 2) is a 13-diketone, which incorporates structural features of both reactants - ketone donor and aldehyde acceptor (see below, Scheme 3) - in the aldol reaction of interest. In favorable cases the hapten reacts with the primary amino-group of a lysine residue in the complementary-determining region of an antibody to form a Schiffbase 5, which readily tautomerises to the more stable vinylogous amide 6. 

A simple, fast and specific color test for urea nitrate was reported recently by Almog et al. It is based on the reaction between urea nitrate and ethanolic solution ofp-dimethylaminocinnamaldehyde (p-DMAC) (9) under neutral conditions [91]. A red pigment is formed within 1 min from contact. Its structure has also been determined by the same group, by X-ray crystallography [92]. It appears to be a resonance hybrid between a protonated Schiffbase (10) and a quinoid system (10a) (Eq. (14)). The limit of detection on filter paper is 0.1 mg/cm. Urea itself, which is the starting material for urea nitrate, does not react with p-DMAC under the same conditions. Other potential sources of false-positive response such as common fertilizers, medications containing the urea moiety and various amines, do not produce the red pigment with p-DMAC. 

Soloshonok and co-workers have developed a method for the synthesis of a-(perfluoro-alkyl)amines from perfluoroalkyl carbonyl compounds by a transamination involving an azomethine a/omethine (Schiffbase) isomerization. They call this method a biomimetic, base-catalyzed 1,3-proton shift reaction, and have applied it to perfluoroaldehydes,12-15 perfluoroalkyl ketones,12 18 / -(perfluoroalkyl)-/l-oxo esters,15 16 19 24 and - -( perfluoroalkyl)-a-oxo es-ters2 " -26 to synthesize the corresponding a-(perfluoroalkyl)amincs, / -(perfluoroalkyl )-/i-amino acids, and 3 -(perfluoroalkyl)- x-amino acids. 

Virtually all types of metal ions have been complexed with macrocyclic ligands.2-7 Complexes of transition metal ions have been studied extensively with tetraaza macrocycles (Chapter 21.2). Porphyrin and porphyrin-related complexes are of course notoriously present in biological systems and have been receiving considerable investigative attention (Chapter 22).8 Macrocyclic ligands derived from the Schiffbase and template-assisted condensation reactions of Curtis and Busch also figure prominantly with transition metal ions.6,7 The chemistry of these ions has been more recently expanded into the realm of polyaza, polynucleating and polycyclic systems.9 Transition metal complexes with thioether and phosphorus donor macrocycles are also known.2... 

Figure 9.11 demonstrates the Schiffbase formation reaction for class II aldolases, which are mainly found in prokaryotes E.coli aldolase uses a zinc ion to ionize the carbonyl group of DHAP (Alan Berry, University of Leeds) it is now Figure 9.12. 

To a solution of benzaldehyde, N-(tert-butoxycarbonyl)imine (10.7 mg, 52.3 pmol), tert-butyl glycinate benzophenone Schiffbase (14.8 mg, 50.1 pmol) and catalyst (5.0 mg, 5.0 pmol) in fluorobenzene (0.5 mL) was added Cs2C03 (32.6 mg, 100.1 pmol) at -30 °C. After stirring for 19 h, the reaction was quenched by the addition of water. The water layer was extracted three times with EtOAc. The combined organic layer was dried over MgS04 and concentrated. The residue was purified by column chromatography on silica gel (hexane ether, 10 1 as eluent) to give the product (24.5 mg, 98%). 

Increasingly sophisticated catalytic domains have been synthesized and used as adducts to the framework polymers. These synthetic macromolecules show substantially enhanced catalytic effects on hydrolytic reactions, decarboxylation, Schiffbase hydrolysis, aromatic nucleophilic substitution, and oxidation [63-69]. Several of these synthetic polymers are effective peptidases and nucleases. 

Mechanistically, the antibody aldolases resemble natural class I aldolase enzymes (Scheme 4.7) [52]. In the first step of a condensation reaction, the s-amino group of the catalytic lysine reacts with a ketone to form a Schiffbase. Deprotonation of this species yields a nucleophilic enamine, which condenses with electrophilic aldehydes in a second step to form a new carbon-carbon bond. Subsequent hydrolysis of the Schiffbase releases product and regenerates the active catalyst. 

Dilution has a significant effect in reducing the rate of the reaction, and the formation of Schiffbases is slowed down, although not entirely stopped once the compound has been diluted in alcohol. Methyl anthranilate occurs naturally in many essential oils together with aldehydes such as citral without forming Schiffbases owing to the low concentration of both materials. 

While the majority of macrocycles formed by this type of Schiffbase condensation reaction are derived from pyridine containing fragments, considerable attention has also been devoted to the use of other heterocycles, including five membered ones, as the primary macrocyclic precursors. Although these latter ligands are for the most part not completely conjugated, they form an important group of expanded porphyrin-type macrocycles. It is for this reason that they are included in the present review,... 

Reaction of [W(CN)302]" with salicylaldehyde and 1,2-diaminoethane (precursors of the Schiffbase salenH2) afforded [Wi 0(CN)(salen)]2-. 

Soluble, swellable and macroporous chelate polymers with coordinative and covalent bonds (Chaps. 2, 3) may be prqiared. Structure investigations are in most cases possible with conventional method. The advantage of coordinative tmding is the ease of preparation. But on the other side aich a bond is not so strong when compared with a covalent one. So the application must decide between coordinative or covalent bond. Reversible binding of small molecules, catalysis and photoredox reactions may be important. Cheaper, easier to prepare and more stable phthalocyanines, oximes and Schiffbase chelates will find higher practical interest then porphyrins. 

Asymmetric ring-opening of saturated epoxides by organocuprates has been studied but only low enantioselectivities (< 15% ee) have so far been obtained [49 SO]. Muller et al. for example, have reported that the reaction between cydohexene oxide and MeMgBr, catalyzed by 10% of a chiral Schiffbase copper complex, gave trafxs-2-methylcydohexanol in 50% yield and with 10% ee [50]. 

The basic approach to prepare Co(II)-complexes of salen (N,lSr-bis(salicylidene)ethylene-diamine)-type molecules is the flexible ligand method [9]. In this process the Schiffbase ligand can diffuse by twisting into the zeolite where it becomes too large to exit by complexation with the cobalt ion. The flexible ligand method, however, was not usefiil for the preparation of Co-salophen/ zeolite catalyst, because the product was inactive in the oxidation reactions. The salophen molecule does not seem to be flexible enough and can not get into the zeolite to produce the suitable complex in the supercage. 

As was true in step 4 of glycolysis (Figure 29.4), this aldol reaction actually takes place not on the free ketone but on an imine (Schiffbase) formed by reaction of dihydroxyacetone phosphate with a side-chain -NH2 group on the enzyme. Loss of a proton from the neighboring carbon then generates an enamine (Section 19.9), an aldol-like reaction ensues, and the product is hydroiyzed. 

Hydroamination reactions involving alkynes and enantiomerically pure chiral amines can produce novel chiral amine moieties after single pot reduction of the Schiffbase intermediate 82 (Scheme 11.27) [123]. Unfortunately, partial racemiza tion ofthe amine stereocenter was observed with many titanium based hydroamina tion catalysts, even in the absence of an alkyne substrate. No racemization was observed when the sterically hindered Cp 2TiMe2 or the constrained geometry catalyst Me2Si(C5Me4)(tBuN)Ti(NMe2)2 was used in the catalytic reaction. Also, the addition of pyridine suppressed the racemization mostly. 

Ooi and Maruoka developed an efficient phase transfer catalyst (46a-e), which consisted of chiral N-spiro ammonium salts with binaphthalene skeleton. 3,3 -(3,4,5-Trifluorophenyl)ammonium salt (46e) provided a perfect stereoselection in benzylation of benzophenone Schiffbase of glycine terf-butyl ester (47) (Scheme 5.13, Table 5.5) [19]. The perfect stereoselective alkylation is applicable for a variety of alkyl bromides in the presence of 1 mol% of the catalyst (46e). Not only monoalkylation but also the consecutive double alkylation of 49 was successful to give 50 in excellent enantioselectivities (Scheme 5.14) [20]. The protocol is useful for the enantioselective aldol reaction of 47 with aldehyde (51) [21] and a-imino ester [22], in which catalysts (46f) and (46g) were effective (Scheme 5.15) [23]. 

Pyridoxal phosphate, a derivative of vitamin Be, acts as coenzyme in transamination and decarboxylation reactions. In a transamination reaction the aldehyde group of pyridoxal phosphate first forms a Schiffbase with the amino group of the amino acid, which is then converted to keto acid. Pyridoxal phosphate is thereby converted to pyridoxamine phosphate which transfers the amino group to an other keto acid to form the corresponding amino acid. 

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