Pyrrole base strength

As with the reaction of pyrroles, diazoles and triazoles react with propargyl bromide to yield TV-substituted products and, depending upon the base strength, either TV-prop-2-ynylazoles or allenic derivatives are formed [30]. Generally, with potassium carbonate under soliddiquid two-phase conditions at room temperature in the absence of a solvent, the prop-2-ynyl compounds are formed as sole products, whereas with solid potassium hydroxide at elevated temperatures the allenes are obtained as the major products. Benztriazole produces a mixture of the N1- and N2-prop-2-ynyl, and N2-allenic derivatives, whereas with potassium hydroxide only the N -allenic derivative is obtained. The alkynes readily isomerize to the allenes in the presence of base and the quaternary ammonium salt, or upon treatment with methanolic sodium hydroxide. A series of l-(alk-2-ynyl)imidazoles have been prepared, as intermediates in the synthesis of imidazopyridines [31 ] and the reaction of 3-hydroxymethylpyrazoles with propargyl bromide leads to pyrazolooxazines [32]. 

Base strengths. The pKa values of pyrroles and benzopyrroles are given in Table 2. These basicities are lower than those of enamines in consequence of the loss of aromaticity which accompanies protonation on the ring... 

We have recently studied systematically the Lewis basicity of zeolites using pyrrole as a probe molecule. Pyrrole has H-donor properties and adsorbs on basic zeolites forming NH—O bridges. The NH stretching vibration was shown by Barthomeuf [51-53] and others [54] to be a measure of the Lewis base strength of 0 in zeolites. 

Table 24.1 lists the pK s of some ammonium ions and indicates there is a substantial range of amine basicities. Most simple alkylamines i similar in their base strength, with for their ammonium ions in the i row range 10-11. Ao nmines, however, such as aniline, are considerably le basic than alkylamines, as are the heterocyclic amines pyridine and pyrrole. 

The Lewis acid-base properties of zeolites received a growing interest recently. A series of works " suggested that the infrared and XPS spectra of adsorbed pyrrole can characterize both the Lewis basicity and the Lewis acidity of alkali-exchanged zeolites. The zeolite base strength decreases with an increase in Si/AI ratio of the framework, and increases when the electropositivity of the counter alkali cation is raised. The Lewis acid strength of counter cations increases with Si/AI ratio and decreases with electropositivity. In other words, the alkali-exchanged zeolites have both Lewis acid and Lewis base centres and provide an easy way to tune up the relative strengths of these two sites. 

Table 7). Hence, no evidence for pronounced effects of differing base strength of pyrrole nitrogens emerges from these data. 

As an example of pyrrole application. Fig. 50 characterizes the basicity of X- and Y-type zeolites and the effect of the charge-compensating cations on the basicity of the adsorbent As a measure of the base strength, the shift of the NH stretching band of the probe is used (cf.[803]). 

Like pyridine and imidazole, pyrrole is an aromatic heterocycle, but it is not nearly as basic as pyridine or imidazole. Pyrrole s lack of base strength can be understood by noticing that the lone pair on the nitrogen atom is in a 2p orbital and is part of the aromatic sextet of electrons. As a consequence, a protonated pyrrole cannot maintain aromaticity because the protonated nitrogen would be sp hybridized and there would be only 4 tt electrons remaining (in violation of two of Hiickel s aromaticity rules). A loss of aromaticity is energetically very costly and severely limits the ability of pyrrole to accept a proton despite its structural similarity to pyridine and imidazole. 

The base strengths of pyrrole and some methylpyrroles in aqueous sulphuric acid have been determined by a method which amounts to the definition of an acidity function specifically for these compounds246-47 These and other results are collected in Table 4A. An earlier value a for pyrrole was much too high247. Values of pif obtained by use of buffer solutions are not strictly comparable with those for sulphuric acid solutions . Pyrrole is clearly a very weak base, and alkyl groups are markedly base-strengthening. The effect of methyl substitution at a particular site upon protonation at another site is roughly constant . xhe sites of protonation have already been discussed. 

Pyrrole is a 7r-electron excessive compound and reacts at the 2-position with electrophiles more rapidly than benzene. However, depending on the acid strength, either the free base or the conjugate acid is the reacting species. 

The pH dependence of die interconversion kinetics, equilibrium, and solubilities of die lactone and hydroxyacid forms of calcium (R-(R, R ) )-2-(4-duorophenyl)-p,5-dihydroxy-5-(l-methylethyl)-3-phenyl- 4r((phenylamino)-carbonyl)-lH-pyrrole-l-heptanoate (CI-981 atorvastatin calcium) are described. Over a pH range of 2.1-6.0 and at 30 °C, the apparent solubility of die sodium salt of CI-981 increases about 60-fold, and die profile yields a pKa for die terminal carboxyl group of 4.46. In contrast, over a pH range of 2.3-7.7 at the same temperature, die apparent solubility of die lactone form of CI-981 varies lidle, and die mean solubility is 1.34 meg/ml. The kinetics of interconversion and die equilibrium between the hydroxyacid and lactone forms have been studied as a function of pH, buffer concentration, and temperature at a fixed ionic strength. The rate constant for lactone formation is well described by specific acid-catalyzed and spontaneous lactonization padiways, whereas die rate constant for lactone hydrolysis is well described by specific acid-, water-, and specific base-catalyzed padiways."... 

Micro calorimetric measurements of ammonia, pyrrole, dimethylether, and acetonitrile adsorption unveiled various strength distributions among the acid sites population of Y-type zeoUtes with various Si/Al ratios [85]. Ammonia proved to be a reliable probe when only BrOnsted acid sites were investigated. Dimethylether, a very weak base, did not appear to be any better than ammonia to reveal the inhomogeneity of one particular acid sites population, whereas pyrrole appeared as a rather acidic probe which helped visualize the basicity difference between the parent material and the dealuminated samples. Acetonitrile proved to be a reUable probe to monitor quantitatively and qualitatively Lewis acidity. 

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