Of pyrrole

Hantzsch synthesis The formation of pyridine derivatives by the condensation of ethyl acetoacetate with ammonia and an aldehyde. Also applied to similar syntheses of pyrroles. 

C4H N. Almost colourless, ammonia-like liquid, b.p. 88-89 C, which fumes in air. Strong base. It occurs naturally in tobacco leaves, but is made industrially by hydrogenation of pyrrole. 

Ambroseo J R and Hoohstrasser R M 1988 Pathways of relaxation of the N-H stretohing vibration of pyrrole in liquids J. Chem. Phys. 89 5956-7... 

The preparation of 2 4-dimethyl-3 5-dicarbethoxypyrrole (II) is an example of the Knorr synthesis of pyrrole derivatives, involving the reaction of an -aminoketone (or a derivative thereof) with a reactive methylene ketone (or a derivative thereof). The stages In the present synthesis from ethyl acetoacetate (I) may be represented as follows ... 

If one heats acetone and pyrrole in the presence of catalytic amounts of acid, so-called acetone pyrrole is formed in over 80%i yield. This colorless, macrocyclic compound contains four pyrrole units which are connected by dimethylmethylene bridges, ft is formed by electrophilic-a-substitution of pyrrole by acetone, acid-catalyzed oligomerization, and spontaneous. 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

In pyrrole on the other hand the unshared pair belonging to nitrogen must be added to the four tt electrons of the two double bonds m order to meet the six tt elec tron requirement As shown m Figure 11 166 the nitrogen of pyrrole is sp hybridized and the pair of electrons occupies a p orbital where both electrons can participate m the aromatic tt system... 

Stability. Diesel fuel can undergo unwanted oxidation reactions leading to insoluble gums and also to highly colored by-products. Discoloration is beheved to be caused by oxidation of pyrroles, phenols, and thiophenols to form quiaoid stmctures (75). Eventually, these colored bodies may increase in molecular weight to form insoluble sludge. 

Iron Porphyrins. Porphyrias (15—17) are aromatic cycHc compouads that coasist of four pyrrole units linked at the a-positions by methine carbons. The extended TT-systems of these compounds give rise to intense absorption bands in the uv/vis region of the spectmm. The most intense absorption, which is called the Soret band, falls neat 400 nm and has 10. The TT-system is also responsible for the notable ring current effect observed in H-nmr spectra, the preference for planar conformations, the prevalence of electrophilic substitution reactions, and the redox chemistry of these compounds. Porphyrins obtained from natural sources have a variety of peripheral substituents and substitution patterns. Two important types of synthetic porphyrins are the meso-tetraaryl porphyrins, such as 5,10,15,20-tetraphenylporphine [917-23-7] (H2(TPP)) (7) and P-octaalkylporphyrins, such as 2,3,7,8,12,13,17,18-octaethylporphine [2683-82-1] (H2(OEP)) (8). Both types can be prepared by condensation of pyrroles and aldehydes (qv). 

Endo adducts are usually favored by iateractions between the double bonds of the diene and the carbonyl groups of the dienophile. As was mentioned ia the section on alkylation, the reaction of pyrrole compounds and maleic anhydride results ia a substitution at the 2-position of the pyrrole ring (34,44). Thiophene [110-02-1] forms a cycloaddition adduct with maleic anhydride but only under severe pressures and around 100°C (45). Addition of electron-withdrawiag substituents about the double bond of maleic anhydride increases rates of cycloaddition. Both a-(carbomethoxy)maleic anhydride [69327-00-0] and a-(phenylsulfonyl) maleic anhydride [120789-76-6] react with 1,3-dienes, styrenes, and vinyl ethers much faster than tetracyanoethylene [670-54-2] (46). 

Pyrroles may be ring-expanded to pyridines in reactions having a greater academic than practical interest. Treatment of pyrrole with chloroform and sodium ethoxide (in effect, with dichlorocarbene, CCl2) gives a low yield of 3-chloropyridine [626-60-8]. A much better yield (33%) is obtained if chloroform and pyrrole are heated together in the vapor phase at 550°C some 2-chloropyridine (17) is also formed (71). 

Pyrrole is a colorless, slightly hygroscopic Hquid which, if fresh, emits an odor like that of chloroform. However, it darkens on exposure to air and eventually produces a dark brown resin. It can be preserved by excluding air from the storage container, preferably by displacement with ammonia to prevent acid-catalyzed polymerization. A review of the physical and theoretical aspects of pyrrole is found in Reference 4. Some physical properties of pyrrole are Hsted in Table 1. 

Many of the physical characteristics of pyrrole indicate at least partial association. In particular, the boiling point is 98°C higher than that of furan. It has been postulated that various associated dimeric and higher stmctures occur because of hydrogen bonding (9,10). 

Knorr Synthesis. Condensation of an a-aminoketone with a carbonyl compound was first reported by Knott (20). This reaction and its modifications are among the most important and widely used methods for the synthesis of pyrroles. 

Hantzsch and Feist Syntheses. The Hant2sch synthesis of pyrroles iavolves condensation of an a-haloketone (10) with a p-keto ester (6) ia the presence of ammonia or an amine (22). 

Paal-Knorr Synthesis. The condensation of a 1,4-diketone, for example, with ammonia or a primary amine generally gives good yields of pyrroles many syntheses have been reported (24). The lack of avaHabitity of the appropriate 1,4-diketone sometimes limits the usefiilness of the reaction. 

N-Alkylpyrroles may be obtained by the Knorr synthesis or by the reaction of the pyrrolyl metallates, ie, Na, K, and Tl, with alkyl haUdes such as iodomethane, eg, 1-methylpyrrole [96-54-8]. Alkylation of pyrroles at the other ring positions can be carried out under mild conditions with allyhc or hensylic hahdes or under more stringent conditions (100—150°C) with CH I. However, unless most of the other ring positions are blocked, poly alkylation and polymerisation tend to occur. N-Alkylation of pyrroles is favored by polar solvents and weakly coordinating cations (Na", K" ). More strongly coordinating cations (Li", Mg " ) lead to more C-alkylation. 

N-Acylation is readily carried out by reaction of the alkaU metal salts with the appropriate acid chloride. C-Acylation of pyrroles carrying negative substituents occurs in the presence of Friedel-Crafts catalysts. Pyrrole and alkylpyrroles can be acylated noncatalyticaHy with an acid chloride or an acid anhydride. The formation of trichloromethyl 2-pyrryl ketone [35302-72-8] (20, R = CCI3) is a particularly useful procedure because the ketonic product can be readily converted to the corresponding pyrrolecarboxyUc acid or ester by treatment with aqueous base or alcohoHc base, respectively (31). 

The most generally useful method for acylation or formyl a ti on of pyrroles is the Vil smeier-Ha ack reaction (32,33). The pyrrole is treated with the phosphoryl complex of A/ A -dialkjlamide and the intermediate imine salt is hydroly2ed. 

Nitration of pyrroles by the usual methods leads to extensive degradation. However, nitration can be achieved with an equimolar nitric acid—acetic anhydride mixture at low temperatures. In the case of pyrrole, the reaction leads predominandy to substitution at the -position (34), ie, in the following 51% 3-nitropyrrole [5930-94-9] (21) and 13% 2-nitropyrrole [5919-26-6] (22). 

Ring openings of pyrrole commonly occur at the carbon—nitrogen bond. Treatment of pyrrole or 2,5-dimethylpyrrole [625-84-3] (23, R = CH3) with hydroxjlamine leads to ring opening and formation of dioximes (31) (39). 

Reaction of pyrrole with carbenes yields enlarged ring systems as well as 2-formylpyrrole [1003-29-8] (40). 

Analytical and Test Methods. In addition to the modem spectroscopic methods of detection and identification of pyrroles, there are several chemical tests. The classical Runge test with HCl yields pyrrole red, an amorphous polymer mixture. In addition, all pyrroles with a free a- or P-position or with groups, eg, ester, that can be converted to such pyrroles under acid conditions undergo the Ehrlich reaction with p-(dimethylamino)henzaldehyde to give purple products. 

Both pyrrole and indole react with selenium dioxide in the presence of nitric acid to give a deep violet solution. Very small quantities (ca 4 of pyrrole can be detected by this method. 

The a-hydioxypyiioles, which exist piimadly in the tautomeric pyiiolin-2-one form, can be synthesized either by oxidation of pyrroles that ate unsubstituted in the a-position or by ting synthesis. P-Hydtoxypyttoles also exist primarily in the keto form but do not display the ordinary reactions of ketones because of the contributions of the polar form (25). They can be teaddy O-alkylated and -acylated (41). 

Polypyrroles. Highly stable, flexible films of polypyrrole ate obtained by electrolytic oxidation of the appropriate pyrrole monomers (46). The films are not affected by air and can be heated to 250°C with Htde effect. It is beheved that the pyrrole units remain intact and that linking is by the a-carbons. Copolymerization of pyrrole with /V-methy1pyrro1e yields compositions of varying electrical conductivity, depending on the monomer ratio. Conductivities as high as 10 /(n-m) have been reported (47) (see Electrically conductive polymers). 

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). 

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