Applications of benzotriazole methodology in heterocycle ring synthesis and substituent introduction and modification

Applications of benzotriazole methodology for the preparation of heterocyclic compounds are reviewed. The characteristic advantages of benzotriazole as a synthetic auxiliary are first briefly considered. This is followed by a summary of its use in ring synthesis in which the construction of small; five-membered; six-membered; and larger heterocyclic rings using benzotriazole methodology are each examined separately. Finally, consideration of the use of benzotriazole in the ring annulation - particularly benzannulation - of heterocycles. Subsequent sections deal with the introduction of substituents into aromatic heterocycles; the ring substitution of saturated heterocycles; and benzotriazole assisted modification of heterocyclic substituents. The present review supplements a recent comprehensive review of benzotriazole chemistry [1] which covers the literature through 1996.     

CORRELATION BETWEEN THE BINDING OF FORMATE AND DECREASED RATES OF CHARGE TRANSFER THROUGH THE PHOTOSYSTEM II QUINONES

Abstract— The binding parameters of bicarbonate to the thylakoid membrane at different formate concentrations have been established [Stemler and Murphy (1983) Photochem. Phorobiol. 38, 701–707]. Based on these parameters, predictions could be made concerning the effects of bicarbonate and formate on photosynthetic electron flow. In this work these effects of various concentrations of bicarbonate and formate are measured and compared to predictions from the binding study. Electron flow is measured between Q_A and Q_B (the primary and secondary quinone acceptors) and Q_B and the plastoquinone pool. Also, these same concentration effects are determined for silicomolybdate supported oxygen evolution. It is found that the results of the bicarbonate binding study are in good agreement with the concentration dependence determined for the quinone reactions, as well as the silicomolybdate reaction. The bicarbonate concentrations required for half-maximal effects are approximately 100 μM, 300 μM and 1.3 mM in the presence of 0, 20 mM and 100 mM formate, respectively. It is concluded that a hierarchy of possible electron flow rates exist. The slowest rates occur when formate is bound. A substantially higher rate occurs when neither formate nor bicarbonate (< 2 μM) are present, but only chloride is present. The highest rates of electron flow occur when bicarbonate is bound. The Q_A- Q_B→ Qa Qb^? Qa^? Qb^2– PQ → Q_a Q_b- PQ^2–, and the silicomolybdate reactions all have the same concentration dependence on formate and bicarbonate. From this it is concluded that a single binding site for formate and bicarbonate affect all of these reactions. The possibility that multiple sites exist with approximately equal affinities for bicarbonate cannot be excluded.     

Pyrrole studies part 41. Reactivity of 3,4-diformyl-2,5-dimethylpyrrole with diaminoalkanes. An unusual formation of 2-azafulvenes

3,4-Diformyl-2,5-dimethylpyrrole (1) reacts with ,ω-diamino-alkanes, NH₂(CH₂)_nNH₂t' to form either the potentially tautomeric 2:2 macrocyclic adduct (7a) (8), when N = 2, or the potentially tautomeric 1:1 bicyclic adduct (18) (19), when N = 4, 5, 6, and 12. ¹H and ¹³C N.m.r. spectral data indicate that the 2-azafulvene structures predominate for both types of cycloadducts. Only polymeric material was obtained when N = 3.     

Understanding binding affinity: a combined isothermal titration calorimetry/molecular dynamics study of the binding of a series of hydrophobically modified benzamidinium chloride inhibitors to trypsin

The binding of a series of p-alkylbenzamidinium chloride inhibitors to the serine proteinase trypsin over a range of temperatures has been studied using isothermal titration (micro)calorimetry and molecular dynamics simulation techniques. The inhibitors have small structural variations at the para position of the benzamidinium ion. They show small differences in relative binding affinity but large compensating differences in enthalpy and entropy. Binding affinity decreases with increased branching at the first carbon but increases with increasing the length of a linear alkyl substituent, suggesting that steric hindrance and hydrophobic interactions play dominant roles in binding. Structural analysis showed that the backbone of the enzyme was unaffected by the change of the para substituent. In addition, binding does not correlate strongly with octanol/water partition data. To further characterize this system, the change in the heat capacity on binding, the change in solvent-accessible surface area on binding, the effect of inhibitor binding on the hydration of the active site, the pK(a) of His57, and interactions within the catalytic triad have been investigated. Although the changes in inhibitor structure are small, it is demonstrated that simple concepts such as steric hindrance, hydrophobicity, and buried surface area are insufficient to explain the binding data. Other factors, such as access to the binding site and the cost of dehydration of the active site, are of equal or greater importance.     

A simplified synthesis of the hexamethylplatinate(IV) ion

Tetra-n-butylammonium hexachloroplatinate (IV) reacts with lithium methyl/lithium iodide in ether to give a solution containing lithium hexamethylplatinate (IV). With lithium methyl/lithium bromide in ether however, tetrabutylammonium hexamethylplatinate (IV) is precipitated together with lithium halides. Solid [Bu₄N)₂[Pt(Ch₃)₆] is stable under nitrogen at room temperature, but ether solutions of [Pt(Ch₃)₆]^2- decompose in a few minutes at room temperature in the absence of excess lithium methyl.     

A general and efficient synthesis of sulfonylbenzotriazoles from N-chlorobenzotriazole and sulfinic acid salts

One-pot reactions of sulfinic acid salts (produced from organometallic reagents with SO2) with N-chlorobenzotriazole gave the corresponding N-alkane-, N-arene-, and N-heteroenesulfonylbenzotriazoles 3a-j in 41-93% yields. Reagents 3a-j are efficient sulfonylating agents, reacting at 20-80 degrees C with various primary and secondary aliphatic amines to yield the corresponding sulfonamides in 64-100% yields.     

Bifunctional pincer-type organometallics as substrates for organic transformations and as novel building blocks for polymetallic materials

The reactivity of the bifunctionalized ligand NC(Br)N-I 1 [IC(6)H(2)(CH(2)NMe(2))(2)-3,5-Br-4] has been studied as a versatile synthon for organic and/or organometallic synthesis. Chemoselective metalation (M = Pd, Pt, Li) at the C(aryl)-I or C(aryl)-Br bonds was achieved by choosing the appropriate metal precursors. In this way a series of Pt(II) and Pd(II) complexes were prepared that have a second functional group available for further reactions. These Pt(II) and Pd(II) complexes were subjected to a wide range of organic and organometallic reactions, revealing the remarkable stability of their M-C sigma-bond and opening an easy route for the synthesis of mono- and (hetero)bimetallic building blocks. The scope of the chemistry of such building blocks shows that they are good candidates for use in the synthesis of dendrimers, bioorganometallic systems, or polymetallic materials. The X-ray crystal structures of the most representative complexes (2, 3a, 19, 20, and 24) are also reported.     

Flow-injection amperometric determination of oxalate with immobilized oxalate oxidase

Oxalate is immobilized on controlled-pore glass and is used on-line in a glass minicolumn (2.5×25 mm). The hydrogen peroxide formed is detected amperometrically. Oxalate (6×10^?6?9×10^?4 M) is determined in a flowing stream of pH 3.5 citrate (or succinate) buffer. As little as 20 ng (in 40 μl; 5.7×10^?6 M) of oxalate can be detected. Copper inhibition can be removed either by adding EDTA to the carrier stream or incorporating a chelating-resin minicolumn into the flow system prior to the enzyme column.     

Flow-injection determination of sulphite and assay of sulphite oxidase

Sulphite (1–80 × 10^?5 M) in formaldehyde-stabilized solutions is determined by injection into a flowing stream of pH 8.5 phosphate buffer, passing through a mini-column of sulphite oxidase immobilized on controlled-pore glass, with amperometric detection of the hydrogen peroxide produced. Sulphite oxidase (5–100 U l^?) is determined by injection into a flowing stream of formaldehyde-stabilized 2 × 10^?3 M sodium sulphite in pH 8.0 phosphate buffer; hydrogen peroxide is again monitored.