Pyrroles basicity

Prepared by heating ammonium mucate, or from butyne-l,4-diol and ammonia in the presence of an alumina catalyst. The pyrrole molecule is aromatic in character. It is not basic and the imino-hydrogen atom can be replaced by potassium. Many pyrrole derivatives occur naturally, e.g. proline, indican, haem and chlorophyll. 

In the heaviest fractions such as resins and asphaltenes (see article 1.2), metal atoms such as nickel and vanadium are found. They belong in part to molecules in the porphyrine family where the basic pattern is represented by four pyrrolic rings, the metal being at the center of this complex in the form Wi - or V0+ (< 3)... 

Crude oils contain nitrogen compounds in the form of basic substances such as quinoline, isoquinoline, and pyridine, or neutral materials such as pyrrole, indole, and carbazole. 

Even less dangerous in this respeet are the nitrating systems using alkyl nitrates and sodium ethoxide. Noteworthy examples of the use of these less acidic or basic nitrating systems are found in the pyrrole series. 

Pyridine and pyrrole are both weak bases but pyridine is much more basic than pyrrole When pyridine is protonated its unshared pair is used to bond to a proton and... 

Indole is a heterocycHc analogue of naphthalene. The basic reactivity patterns of indole can be understood as resulting from the fusion of an electron-rich pyrrole ring with a ben2ene ring. 

Although only ppm levels of nitrogen are found in the mid-distillates, both neutral and basic nitrogen compounds have been isolated and identified in fractions boiling below 345°C (12). Pyrroles and indoles account for about two-thirds of the nitrogen. The remaining nitrogen is found in the basic pyridine and quinoline compounds. Most of these compounds are alkylated. 

Pyrrole has a planar, pentagonal (C2 ) stmcture and is aromatic in that it has a sextet of electrons. It is isoelectronic with the cyclopentadienyl anion. The TT-electrons are delocalized throughout the ring system, thus pyrrole is best characterized as a resonance hybrid, with contributing stmctures (1 5). These stmctures explain its lack of basicity (which is less than that of pyridine), its unexpectedly high acidity, and its pronounced aromatic character. The resonance energy which has been estimated at about 100 kj/mol (23.9 kcal/mol) is intermediate between that of furan and thiophene, or about two-thirds that of benzene (5). 

Vinyl chloride reacts with sulfides, thiols, alcohols, and oximes in basic media. Reaction with hydrated sodium sulfide [1313-82-2] in a mixture of dimethyl sulfoxide [67-68-5] (DMSO) and potassium hydroxide [1310-58-3], KOH, yields divinyl sulfide [627-51-0] and sulfur-containing heterocycles (27). Various vinyl sulfides can be obtained by reacting vinyl chloride with thiols in the presence of base (28). Vinyl ethers are produced in similar fashion, from the reaction of vinyl chloride with alcohols in the presence of a strong base (29,30). A variety of pyrroles and indoles have also been prepared by reacting vinyl chloride with different ketoximes or oximes in a mixture of DMSO and KOH (31). 

The low basicity of pyrrole is a consequence of the loss of aromaticity which accompanies protonation on the ring nitrogen or on carbon 2 or carbon 3 of the ring. The thermodynamically most stable cation is the 2H-pyrrolium ion, and the p/sTa for protonation at C-2 has been recorded as -3.8 the corresponding pK values for protonation at C-3 and at nitrogen are -5.9 and ca. -10 (Scheme 7). 

A comparison of the relative basicities of pyrrole, furan and thiophene may be made by comparing the pK values of their 2,5-di-t-butyl derivatives, which were found to be -1.01, —10.01 and —10.16, respectively. In each case protonation was shown by NMR to occur at position 2. The base-strengthening effect of alkyl substitution is clearly apparent by comparison of pyrrole and its alkyl derivatives, e.g. A-methylpyrrole has a pKa. for a-protonation of -2.9 and 2,3,4,5-tetramethylpyrrole has a pK of 4-3.7. In general, protonation of a-alkylpyrroles occurs at the a -position whereas /3-alkylpyrroles are protonated at the adjacent a-position. As expected, electron-withdrawing groups are base-weakening thus A-phenylpyrrole is reported to have a p/sTa of -5.8. The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

Although it has not been possible to study the protonation of isoindole itself, it is clear that isoindoles are more basic than indoles or pyrroles. For example, 2,5-dimethyl-1,3-diphenylisoindole (40) has a p/sTa of 4-2.05 protonation of isoindoles occurs at positions 1 or 3. The pK for protonation of indolizine (10) at position 3 is 4-3.94 and that for carbazole (41) for protonation on nitrogen is estimated at -6.0. 

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

Pyrrole, 2-aeetyl-l-(2-hydroxyethyl)-5-nitro-cyelization, 4, 74 ipso substitution, 4, 243 Pyrrole, 2-aeetyl-l-methyl-dipole moment, 4, 194 photocyelization reaetions with 2,3-dimethylbut-2-ene, 4, 269 Pyrrole, 3-acetyl-4-methyl-Vilsmeier-Haaek formylation, 4, 222 Pyrrole, 2-aeetyl-3-nitro-reduction, 4, 297 Pyrrole, aeyl-basicity, 4, 207 isomerization, 4, 208 oximes... 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

VV -values for bromoform and pyrrole, acidic liquids, against poly(vinyl chloride), an acidic polymer, and dimethyl sulfoxide, a predominantly basic liquid, against polyfmethyl methacrylate), a basic polymer, but large values for the acidic liquids against PMMA and the basic liquid against PVC. 2-Iodoethanol, a bifunctional liquid, showed appreciable -values with both polymers. Despite these results in line with expectations, other results based on wettability measurements are not so clear-cut. For example, Vrbanac [94] found significant apparent acid-base interactions of various aromatic liquids against poly(ethylene), presumably a neutral substrate. 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

---