77-Nitrophenyl picolinate

In 1965, Breslow and Chipman discovered that zinc or nickel ion complexes of (E)-2-pyridinecarbaldehyde oxime (5) are remarkably active catalyst for the hydrolysis of 8-acetoxyquinoline 5-sulfonate l2). Some years later, Sigman and Jorgensen showed that the zinc ion complex of N-(2-hydroxyethyl)ethylenediamine (3) is very active in the transesterification from p-nitrophenyl picolinate (7)13). In the latter case, noteworthy is a change of the reaction mode at the aminolysis in the absence of zinc ion to the alcoholysis in the presence of zinc ion. Thus, the zinc ion in the complex greatly enhances the nucleophilic activity of the hydroxy group of 3. In search for more powerful complexes for the release of p-nitrophenol from 7, we examined the activities of the metal ion complexes of ligand 2-72 14,15). 

Table 2. Association constants (K) and second-order rate constants (kL and kc) for p-nitrophenol release from p-nitrophenyl picolinate 1 in the presence of ligand (L) and metal ion (M)a-b...

We have disclosed that the ligands 4c, 10, and 77, when complexed with a metal ion such as Zn2 +, Ni2+, or Co2+, become highly active toward the hydrolysis of p-nitrophenyl picolinate (7). The catalysis is most likely to occur through formation of a ternary complex in the transition state or in reactive intermediates. The metal ion in such a complex serves to activate the ligand hydroxyl group for nucleophilic attack and to orient the substrate into a favorable position to undergo the reaction. 

Table 3. Kinetic parameters for the release of p-nitrophenol from p-nitrophenyl picolinate 1 under micellar conditions of CTAB...

Table 4. Pseudo-first-order rate constants (kob,d) for p-nitrophenol release from p-nitrophenyl picolinate...

Large rate accelerations have been observed in the metal ion-promoted hydrolysis of some lactams and these reactions are considered in Section 61.4.10. Other investigations have dealt with divalent metal ion-catalyzed hydrolysis of p-nitrophenyl picolinate in the presence of imidazoles and pyridines having hydroxyl groups in their side chains,226 the zinc(II)-facilitated hydrolysis of esters of 2-hydroxy acids227 and the metal ion-promoted hydrolysis of methyl 2-( JV-acetylhydrazono) propanoate.228... 

Sigman and Jorgenson490 have found that zinc(II) catalyzes the transesterification reaction between N- (/3-hydroxy ethyl) ethylenediamine and 4-nitrophenyl picolinate. This reaction involves a reactive mixed ligand complex (152) in which the zinc(II) ion perturbs the p/fa of the hydroxyethyl group of N-(/3-hydroxyethyl)ethylenediamine to provide a high effective concentration of the nucleophile. Intramolecular nudeophlic attack then occurs at the carbonyl group of p-nitrophenyl picolinate. This system provides a somewhat unique example of intramolecular... 

In this reaction, the incoming alkoxide group is almost certainly co-ordinated to the metal centre in the key stages of the reaction. A particularly elegant demonstration of this is seen in the zinc(n) catalysed transesterification of 4-nitrophenyl picolinate with HO(CH2)2NH(CH2)2NH2 (Figs. 5-87 and 5-88). In the initial step of the reaction, an intermediate complex 5.38 may be isolated (Fig. 5-87). 

Tagaki et al. [24] and Fomasier et al. [25] reported another type of metallomicelle attached with a metal-bound alkoxide nucleophile. Tagaki s zinc(II) and copper(II) complexes (with possible structures 6a and b) promoted the hydrolysis of 4-nitrophenyl picolinate in a comicellar system with hexadecyl trimethy-lammonium bromide. However, no detailed mechanistic study was reported. Scrimin s zinc(II) and copper(II) complexes (proposed structures 7a and b) also promoted the hydrolysis of 4-nitrophenyl picolinate. A postulated mechanism for the catalytic activity of 7 is shown in Figure 4. An aggregate of 7 more effectively... 

Figure 4 Proposed intramolecular reaction mechanism for 4-nitrophenyl picolinate hydrolysis by Scrimin s metallomicelle 7. See text for details.

Metal-catalysed hydrolysis of / -nitrophenyl picolinate at pH 7.5 was in the order Cu(II) > Ni(II) > Zn(II) > Co(II) > La(III). The probable mechanism is via attack by external HO- on the metal-ion complex (80).80 High catalytic activity in the hydrolysis at pH 7 of p-nitrophenyl picolinate, but not / -nitrophenyl acetate, was displayed by the metal complexes M(2-aminopyridine)2(OAc)2 (M = Zn, Ni), showing that they were good models for hydrolytic metalloenzymes.81... 

Figure 23. Proximity of the charged head group to the binding site in 57 slows chelation of the metal relative to the bolaphile 58. M = Cu11, Zn11 R = para-nitrophenyl picolinate.

Fomasier et al. used metallomicelles formed from bolaphiles and surfactants with only one head group as catalysts for the cleavage for para-nitrophenyl picolinate. [9]... 

The rates of transesteriflcation in anhydrous EtOH at 298 K of 4-nitrophenyl picolinate (12), nicotinate (13), and isonicotinate (14) in the presence of alkali metal ethoxides (EtOM M = K, Na, Li) were compared. Rates were greatest for 4-nitrophenyl picolinate (12) for each alkali metal, and the fastest rate was observed for EtONa. This was attributed to the formation of a flve-membered cyclic transition state (15), of optimal stability for M = Na, which is not possible for (13) or (14). 

In the presence of bis(0,0-dibenzyl)dithiophosphate)nickel(II) the hydrolysis at pH g of p-nitrophenyl picolinate (PNPP) (67) was enhanced more than a 1000-fold. The proposed mechanism of this biomimetic model involved the intramolecular attack of a metal hydroxide species on the bound ester. An unsymmetrical bis-Schiff base Mn(III) complex with a morpholino pendant (68 M=MnCl) also catalysed the alkaline hydrolysis of PNPP (67) very effectively, but was not so effective as a catalyst as Co and Mn complexes with a benzo-lO-aza-crown ether pendant (69 M = MnCl, M = Co). One of the latter (69 M = MnCl) showed an enhancement factor at pH 7.6 of 1.67 X 10 ... 

D. S. Sigman and C. T. Jorgenren (1972), Models for metalloenzymes. The zinc (Il)-catalyzed transesterification of iV-(jS-hydroxyethyl)ethylene-diamine by / -nitrophenyl picolinate. /. Amer. Chem. Soc. 94, 1724-1730. 

Catalytic hydrolysis of p-nitrophenyl picolinate by complexes of Co(II) with triethanolamine, ethylenediamine, and Schiff bases with either benzo-10-azo-crown ether or morpholino pendants and complexes of Ni(II) with ethylenediamine were... 

The rate of hydrolysis of 4-nitrophenyl picolinate or 4-nitrophenyl 2-pyridine carboxylate (1) has been studied at constant pH (maintained by buffers) in the presence of three ligands, MMAr,AT-tetra(2-hydroxyethyl)-l,3-diammopropane (2), N,Af,Af, Af -tetra(2-hydroxyethyl)-l,10-diaminodecane (3), and N,N,N, N -tetra(2-hydroxyethyl)-l,4-diaminoxylene (4) as well as three metal ions, Zn(II),... 

Xiang, Y, Zeng, X., Cheng, S., Li, Y, Xie, J. Accelerated cleavage ofp-nitrophenyl picolinate catalyzed by copper(II) and zinc(II)complexes of D-glucosamine Schiff base in micellar solution. J. Dispersion Sci. Technol. 2000, 27(7), 857-867. 

Tagaki, W., Ogino, K. Tanaka, O., Machiya, K., Kashihara, N., Yoshida, T. Hydrolytic metalloenzyme models miceUar effects on the activation of the hydroxyl groups of N-alkyl-2-(hydroxymethyl)imidazole hgands by in the transacylation of jp-nitrophenyl picolinate. Bull. Chem. Soc. Jpn. 1991, 64(1), 74-80. 

Reaction of the m-nitrophenyl ester of pyridine-2,5-dicarboxylic acid with cyclodextrin (see Section 3) gives a picolinate ester [52] of a cyclodextrin secondary hydroxyl group (Breslow, 1971 Breslow and Overman, 1970) which will bind metal ions or a metal ion-pyridine carboxaldoxime complex. Such a complex will catalyse hydrolysis of p-nitrophenyl acetate bound within the cyclodextrin cavity leading to a rate constant approximately 2000-fold greater at... 

The indolizine nucleus is readily oxidized. No N- oxides have been isolated so far. In the course of many oxidations, ring fission occurs. The reaction has therefore been used in the past for structural elucidation (B-66MI30800). Thus l-(4-nitrophenyl)indolizine on treatment with perhydrol and acetic acid gave picolinic acid N- oxide and 4-nitrobenzoic acid (Scheme 7). 

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