Schiff base formation reaction

Aldehyde particles are spontaneously reactive with hydrazine or hydrazide derivatives, forming hydrazone linkages upon Schiff base formation. Reactions with amine-containing molecules, such as proteins, can be done through a reductive amination process using sodium cyanoborohydride (Figure 14.21). 

Cyanogen bromide, triazine method, cychc trani-2,3-carbonate reaction, carbonylation, periodate oxidation, epoxide activation Curtis azide rearrangement, coupling reagent method, acid anhydride reaction Schiff base formation reaction... 

On-chip Reaction and Analysis. To prove the principle of the monitoring window , the Schiff base formation reaction between 2 and 4 in ethanol (Scheme 11.1) was carried out using the MALDI-chip device equipped with the chip of Figure 11.9. The chip placed on the MALDI sample plate was introduced into the vacuum chamber by load-lock. The first MALDI-TOF mass spectrum was acquired as soon as the plate reached the right spot in the chamber. The analysis started after about 1 min. Ions were extracted from the... 

Aldehyde and acetal Polymers reacted with glutaraldehyde, polysaccharides reacted with periodate Schiff base formation reaction [168,186,187]... 

A cost-efficient synthesis of foHc acid via Schiff base formation is feasible only if 6-formylpterin (23) is readily available. This compound is prepared by the reaction of 2-bromomalondialdehyde dimethylacetal [59453-00-8] (25) with trianainopyrimidinone (10), followed by acetylation and cleavage of the acetal to give compound (23) in 51% overall yield (38). 

There are two distinct groups of aldolases. Type I aldolases, found in higher plants and animals, require no metal cofactor and catalyze aldol addition via Schiff base formation between the lysiae S-amino group of the enzyme and a carbonyl group of the substrate. Class II aldolases are found primarily ia microorganisms and utilize a divalent ziac to activate the electrophilic component of the reaction. The most studied aldolases are fmctose-1,6-diphosphate (FDP) enzymes from rabbit muscle, rabbit muscle adolase (RAMA), and a Zn " -containing aldolase from E. coli. In vivo these enzymes catalyze the reversible reaction of D-glyceraldehyde-3-phosphate [591-57-1] (G-3-P) and dihydroxyacetone phosphate [57-04-5] (DHAP). 

Quite a number of mixed sulfur-nitrogen macrocycles have been prepared, but these have largely been by the methods outlined in Chaps. 4 and 5 for the respective heteroatoms. An alternative method, involves the formation of a Schiff base, followed by reduction to the fully saturated system, if desired. An interesting example of the Schiff base formation is found in the reaction formulated in (6.12). Dialdehyde 14 is added to ethylenediamine in a solution containing ferrous ions. Although fully characterized, the yield for the reaction is not recorded. To avoid confusion with the original literature, we note the claim that the dialdehyde [14] was readily prepared in good yield by reaction of the disodium salt of 3-thiapentane-l, 5-diol . The latter must be the dithiol rather than the diol. 

Recent progress of basic and application studies in chitin chemistry was reviewed by Kurita (2001) with emphasis on the controlled modification reactions for the preparation of chitin derivatives. The reactions discussed include hydrolysis of main chain, deacetylation, acylation, M-phthaloylation, tosylation, alkylation, Schiff base formation, reductive alkylation, 0-carboxymethylation, N-carboxyalkylation, silylation, and graft copolymerization. For conducting modification reactions in a facile and controlled manner, some soluble chitin derivatives are convenient. Among soluble precursors, N-phthaloyl chitosan is particularly useful and made possible a series of regioselective and quantitative substitutions that was otherwise difficult. One of the important achievements based on this organosoluble precursor is the synthesis of nonnatural branched polysaccharides that have sugar branches at a specific site of the linear chitin or chitosan backbone [89]. 

Aldolases catalyze asymmetric aldol reactions via either Schiff base formation (type I aldolase) or activation by Zn2+ (type II aldolase) (Figure 1.16). The most common natural donors of aldoalses are dihydroxyacetone phosphate (DHAP), pyruvate/phosphoenolpyruvate (PEP), acetaldehyde and glycine (Figure 1.17) [71], When acetaldehyde is used as the donor, 2-deoxyribose-5-phosphate aldolases (DERAs) are able to catalyze a sequential aldol reaction to form 2,4-didexoyhexoses [72,73]. Aldolases have been used to synthesize a variety of carbohydrates and derivatives, such as azasugars, cyclitols and densely functionalized chiral linear or cyclic molecules [74,75]. 

The role of Schiff bases formed between pyridoxal phosphate and amino acid residues as intermediate products in many enzymatic reactions is well known and documented. NMR is an excellent tool for studies of the enzymatic processes involving Schiff bases formation. 

Aldehydes and ketones can react with primary and secondary amines to form Schiff bases, a dehydration reaction yielding an imine (Reaction 45). However, Schiff base formation is a relatively labile, reversible interaction that is readily cleaved in aqueous solution by hydrolysis. The formation of Schiff bases is enhanced at alkaline pH values, but they are still not stable enough to use for crosslinking applications unless they are reduced by reductive amination (see below). 

In a fume hood, add 10 pi of 5M sodium cyanoborohydride (Sigma) per ml of reaction solution. Caution cyanoborohydride is extremely toxic. All operations should be done with care in a fume hood. Also, avoid any contact with the reagent, as the 5M stock solution is dissolved in 1 N NaOH. If a higher pH buffer was used for the Schiff base formation, then adjust the solution to pH 7.5 before adding the cyanoborohydride. 

Proteins may be modified with oxidized dextran polymers under mild conditions using sodium cyanoborohydride as the reducing agent. The reaction proceeds primarily through e-amino groups of lysine located at the surface of the protein molecules. The optimal pH for the reductive amination reaction is an alkaline environment between pH 7 and 10. The rate of reaction is greatest at pH 8-9 (Kobayashi and Ichishima, 1991), reflecting the efficiency of Schiff base formation at this pH. 

A selection from the large number of template reactions published following the original report by Curtis will now be described. Schiff-base and related condensations have figured prominently in these reactions. For ease of presentation, it is convenient to separate examples involving non-Schiff-base condensation from those involving Schiff-base formation. The next two subsections are devoted to descriptions of examples from each of these respective types. 

Mechanistically, transamination by the free coenzyme proceeds through a number of discrete steps as illustrated in Fig. 3. The first step of the process, aldi-mine formation (Fig. 3, Step I), is common to all pyridoxal-dependent reactions. The rate and extent of this reaction are influenced by factors including reactant concentrations, the nature of the amino acid, pH, and solvent. However, it is important to realize that the coenzyme itself facilitates Schiff base formation in... 

Structures have been determined for [Fe(gmi)3](BF4)2 (gmi = MeN=CHCF[=NMe), the iron(II) tris-diazabutadiene-cage complex of (79) generated from cyclohexanedione rather than from biacetyl, and [Fe(apmi)3][Fe(CN)5(N0)] 4F[20, where apmi is the Schiff base from 2-acetylpyridine and methylamine. Rate constants for mer fac isomerization of [Fe(apmi)3] " were estimated indirectly from base hydrolysis kinetics, studied for this and other Schiff base complexes in methanol-water mixtures. The attenuation by the —CH2— spacer of substituent effects on rate constants for base hydrolysis of complexes [Fe(sb)3] has been assessed for pairs of Schiff base complexes derived from substituted benzylamines and their aniline analogues. It is generally believed that iron(II) Schiff base complexes are formed by a template mechanism on the Fe " ", but isolation of a precursor in which two molecules of Schiff base and one molecule of 2-acetylpyridine are coordinated to Fe + suggests that Schiff base formation in the presence of this ion probably occurs by attack of the amine at coordinated, and thereby activated, ketone rather than by a true template reaction. ... 

The synthesis pathway of quinolizidine alkaloids is based on lysine conversion by enzymatic activity to cadaverine in exactly the same way as in the case of piperidine alkaloids. Certainly, in the relatively rich literature which attempts to explain quinolizidine alkaloid synthesis °, there are different experimental variants of this conversion. According to new experimental data, the conversion is achieved by coenzyme PLP (pyridoxal phosphate) activity, when the lysine is CO2 reduced. From cadeverine, via the activity of the diamine oxidase, Schiff base formation and four minor reactions (Aldol-type reaction, hydrolysis of imine to aldehyde/amine, oxidative reaction and again Schiff base formation), the pathway is divided into two directions. The subway synthesizes (—)-lupinine by two reductive steps, and the main synthesis stream goes via the Schiff base formation and coupling to the compound substrate, from which again the synthetic pathway divides to form (+)-lupanine synthesis and (—)-sparteine synthesis. From (—)-sparteine, the route by conversion to (+)-cytisine synthesis is open (Figure 51). Cytisine is an alkaloid with the pyridone nucleus. 

Schiff s base formation occurs by condensation of the free amine base with aldehyde A in EtOAc/MeOff. The free amine base solution of glycine methyl ester in methanol is generated from the corresponding hydrochloride and triethylamine. Table 4 shows the reaction concentration profiles at 20-25°C. The Schiffs base formation is second order with respect to both the aldehyde and glycine ester. The equilibrium constant (ratio k(forward)/ k(reverse)) is calculated to be 67. 

Table 4. Reaction kinetics of Schiff base formation...

Aldehyde 82 was extremely reactive and was best isolated as the hydrate 84a. Indeed, recrystallization of the aldehyde 82 from ethanol gave 3-(l-ethoxy-l-hydroxymethyl)fervenulin 84b, while reaction with ethylene glycol gave the cyclic acetal 76a. The reactivity of the aldehyde 82 was exploited by easy Schiff base formation upon reaction with /i-aminobenzoylglutamic acid, a process that was followed by reduction to give the fervenulin-based folic acid analogue 85 <1996JHC949>. 

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