Reactions with Schiff bases

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

FIGURE 18.27 Pyridoxal-5-phosphate forms stable Schiff base adducts with amino acids and acts as an effective electron sink to stabilize a variety of reaction intermediates. 

Figure 15.1 Reactions of formaldehyde with peptides and amino acids. Shown are the four types of reaction products seen when peptides or amino acids are treated with formaldehyde in aqueous solution. These reaction products are methylol (hydroxymethyl) adduct (reaction 15.1), Schiff-base (reaction 15.2), 4-imidazolidinone adduct (reaction 15.3), and one type of methylene bridge [cross-link] (reaction 15.4).

The reaction of the ( -configured Schiff base 315 with benzonitrile oxide gave the 4,5-dihydro-l,2,4-oxadiazole 316 as a single diastereomer (Equation 59) <1999AXC650>. 

Yadav and Kapoor <2003TL8951> reported on a microwave-assisted ring closure leading to novel thiazolo[l,3,5]-triazines, as shown in Scheme 36. This three-component one-pot procedure started from the thiazolyl Schiff base 230, to which ammonium acetate and an aldehyde was added. In the first step, the azomethine moiety of the Schiff base reacted with ammonia to give the zwitterionic first intermediate 231, which underwent deprotonation to the amine 232, and, finally, reaction of this second intermediate with the aldehyde involving the ring-closure step afforded the product 233. It is important to emphasize that the MW-assisted technique ensured high yields (76-88%)... 

The cyclizations of cis- and lrans-2-hydroxymethyl-l-cyclohexylamine and cis- and lram-2-aminomethyl-l-cyclohexanol with 4-nitrobenzaldehyde have been studied by means of H NMR spectroscopy in CDCI3 solution (90ACSA364 91T2229). The time-dependent spectra confirmed that the reactions of all these amino alcohols proceeded via Schiff bases. With the exception of cis-2-hydroxymethyl-l-cyclohexylamine, the thermodynamically more stable perhydrobenzoxazine epimer is also the kinetically favored product. In the former case, from amino alcohol 21 (R = H), the Schiff base 37 with N-outside predominant conformation is formed first due to kinetic control, the less stable epimeric ring form 38 is obtained with N-outside predominant conformation. The thermodynamically controlled product 33 is formed subsequently, via the less stable open-chain form 37, in a slow equilibration process (90ACSA364). 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary iminium salt. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

In contrast, the reaction of SchifFs bases (276) with aryl nitrile sulfides yields 1,2,4-thiadiazolines (277) in very low yields (2-5%) (Equation (42)) <86JCR(S)156>. 

L-Canaline is an ineffective antimetabolite of L-ornithine since it has little ability to antagonize ornithine-dependent reactions. On the other hand, it forms a covalently bound Schiff-base complex with the pyridoxal phosphate moiety of Bg-containing enzymes. As such it is a potent inhibitor of many decarboxylases and aminotransferases that utilize this vitamin. 

It became of interest to see if we could obtain any indication of Schiff base formation with the polymer. Since spectroscopic probes would be obscured with the actual substrate, oxalacetate, because of the progress of the decarboxylation reaction (32), we have examined instead the spectra of oxalacetate-4-ethyl ester in solutions of the same modified poly-(ethylenimine) PEIQ—NH2. Such solutions develop a new absorption band at 290 nm. Furthermore, this band is essentially abolished if NaBH4 is added to the solution (Fig. 21). As is well known, NaBH4 reduces Schiff base linkages to amine groups.43-44... 

Compare the reactions of the / PLP Schiff bases (below) with / those of this ketone... 

There are several classes of alkaloids. Among these are purines such as xanthine and caffeine, ter-penes (Chapter 22), polyketides (Chapter 21), and alkaloids derived from amino acids. The basic amino acids ornithine, arginine, histidine, and lysine as well as the aromatic amino acids, anthranilate, and nicoti-nate are some of the starting materials.199 201 Robinson202 203 in 1917 recognized that many alkaloids are derived directly from aromatic amino acids. He proposed that alkaloids arise from Mannich reactions (Eq. 25-12) in which an amine and an aldehyde (probably through a Schiff base) react with a nucleophilic carbon such as that of an enolate anion. Many of the... 

Reaction of Schiff bases 422 with a mixture of phosphorus oxychloride and dichloroacetic acid in DMF gave triazolopyrimidinones (423) instead of the expected 3,3-dichloroazetidinones (424) (88JHC173). 1,4-Cycloaddition of 422 (R = SMe R1 = Ph) with phenoxyacetyl chloride in the presence of triethylamine gave the dihydro-1,2,4-triazolo[4,3-ajpyrimidinone 425 (88JHC173) (Scheme 82). 

Nishinaga and co-workers isolated a series of stable cobalt(III)-alkyl peroxide complexes such as (170) and (171) in high yields from the reaction of the pentacoordinated Co"-Schiff base complex with the corresponding phenol and 02 in CH2C12. Complex (170 R=Bu ) has been characterized by an X-ray structure. These alkyl peroxide complexes presumably result from the homolytic addition of the superoxo complex Co111—02 to the phenoxide radical obtained by hydrogen abstraction from the phenolic substrate by the CoUI-superoxo complex. The quinone product results from / -hydride elimination from the alkyl peroxide complex (172)561,56,565,566 The quinol (169) produced by equation (245) has been shown to result from the reduction of the CoIU-alkyl peroxide complex (170) by the solvent alcohol which is transformed into the corresponding carbonyl compound (equation 248).561... 

LLB, LiOH, and H2O promoted the direct aldol reaction of glycinate Schiff bases 12 with aldehydes 3, providing access to p-hydroxy-a-amino acid esters 13 (Scheme 4,bottom) [7],... 

Amino groups on proteins may be reacted with the bis-aldehyde compound glutaraldehyde to form activated derivatives able to cross-link with other proteins. The reaction mechanism for this modification proceeds by one of several possible routes. In the first option, one of the aldehyde ends can form a Schiff base linkage with e-amines... 

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