1.3.4- Tris pyrrole

Prodigiosin (Streptorubin B) (192) Tri-pyrrole antibiotic Obatoclax (GX15-070)(193) Oncology Bcl-2 inhibition Phase I/n Gemin X 911,912... 

Subsequent liberation of the tris(pyrrole)pyridine ligand and complexation with Ti gave TiCl(Et8(NC4H2)3(NC5H3)). Alkylation and insertion of CO afforded the complex... 

Prodigiosin.—The final step in the formation of prodigiosin (196) involves condensation of (194) with (195).The origin of the tri-pyrrolic skeleton of this microbial metabolite has been defined recently mainly by use of C-labelled... 

Fig. 3.13 The rotating cone. The molecule is a subporphyrin and consists of a central boron in a tri-pyrrole macrocycle. The subporphyrin itself has the shape of a trigonal dome and exhibits C3 symmetry. Three phenyl substituents at the meso-positions are arranged like a propeller and reduce the symmetry to C3. A further symmetry lowering to Ci is caused by an apical hydroxyl substituent at the boron position, with its hydrogen pointing in the direction of the upper phenyl group...

B(NC4H4)3, tris(pyrrol-1-yl)borane, has been prepared from pyrrole and triethylamine-borane (3 1 mole ratio) by elimination of hydrogen and triethylamine. NMR data (in ppm solvent CDCI3) 6 1B = 27.8, b H = -207, 6 3C = 126.6, 113.6 [12]. 

CisHi2FeN3S6 0.5 CH2CI2, Tris(pyrrole-N-carbodithioato)irondll) dichloromethane solvate, 45B, 1088 Cl5H22MoNg02S6 0.25 CH2CI2 0.25 H2O, Tris(dimethyldithiocarbam-ato)(m-nitrophenyldia2enato)molybdenum methylene chloride solvate hydrate, 46B, 992... 

Berlin and Breitmaier [188] first synthesized a benzene-containing porphyrin analog 325. The method exploits the ready availability of tri- or tris-pyrroles 326 and their ability to condense with m-phthalaldehyde 327 and related compounds to give the macrocycle 325 (Scheme 6.80a). Owing to the presence of the benzene ring in the ring system, 325 does not exhibit aromatic properties. Soon after, Lash [189] reported that the macrocycle obtained by reaction of 326 with 5-formylsalicylaldehyde 328 exists in the keto form 329 as a fairly stable aromatic compound rather than in the phenolic form 330 (Scheme 6.80b). 

Tripodal tris-aldehyde ligand syntones, which have been prepared in [94] using Vilsmeier-Haack-type formylation of the corresponding tris-pyrroles by Scheme 2.82, gave the covalent capsules 124 and 125, the derivatives of ethylene-1,2- and butan-1,4-diamines, respectively. These macrobicyclic hgands encapsulate parent diamines during the template condensation with... 

Condensation of a tris-pyrrole ligand syntone 75 with its diformylated derivative 76 by Scheme 2.101 has been used in [113] for the syn-... 

The replacement of rhodium from a wide range of rhodacycles to form condensed furans, thiophenes, selenophenes, tellurophenes and pyrroles has been widely explored and a range of examples is shown in Scheme 97. The rhodacycles are readily generated from the appropriate dialkyne and tris(triphenylphosphine)rhodium chloride. Replacement of the rhodium by sulfur, selenium or tellurium is effected by direct treatment with the element, replacement by oxygen using m-chloroperbenzoic acid and by nitrogen using nitrosobenzene. 

The Teoc group is introduced onto pyrroles, or indoles with 4-nitrophenyl 2-(tri-methylsilyl)ethyl carbonate and NaH in 61-64% yield. The Teoc group can be removed with Bu4N F in CH3CN. ... 

Perfluoroalkanoyl chlorides and anhydrides are also acylating agents Tri-fluoroacetic anhydride acylates a number of pyrroles, thiophenes, and furans without a catalyst [37, 38, 39] AzuUne can be diacylated without a catalyst in 12 h [40] (equation 26). 

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

In addition to electrophilic attack on the pyrrole ring in indole, there is the possibility for additions to the fused benzene ring. First examine the highest-occupied molecular orbital (HOMO) of indole. Which atoms contribute the most What should be the favored position for electrophilic attack Next, compare the energies of the various protonated forms of indole (C protonated only). These serve as models for adducts formed upon electrophilic addition. Which carbon on the pyrrole ring (C2 or C3) is favored for protonation Is this the same as the preference in pyrrole itself (see Chapter 15, Problem 2)1 If not, try to explain why not. Which of the carbons on the benzene ring is most susceptible to protonation Rationalize your result based on what you know about the reactivity of substituted benzenes toward electrophiles. Are any of the benzene carbons as reactive as the most reactive pyrrole carbon Explain. 

In a series of papers in late 1884 and early 1885, Paal and Knorr demonstrated that several 1,4-dicarbonyls could be transformed into furans, pyrroles, and thiophenes. Paal first discovered this transformation and used it to prepare di-, tri-, and tetrasubstituted furans. For example, dicarbonyl 3 yielded disubstituted furan 4 upon treatment with weak acid. 

Methylpyrrole gives only amorphous polymeric material with HCl or picric acid in ether.In contrast with the pyrroles just mentioned, 2,5- and 3,4-dimethyl-, 2-methyl-5-ethyl-, 3-methyl-4-ethyl-, and 2-methyl-4-ethyl-pyrrole do not form crystalline salts, either monomeric or dimeric, and 2,4-dimethyl- and 4-methyl-2-ethyl-pyrrole form only monomeric salts. The dialkylpyrroles in this latter group all dissolve in aqueous sulfuric acid to form relatively stable solutions (e.g., references 14 and 15). The various tri- and tetra-akylpyrroles are likewise soluble in aqueous mineral acid to form stable solutions, and either do not react with HCl or picric acid... 

Some advances have been made in the Paal-Knorr synthesis of pyrroles by the condensation of primary amines with 1,4-dicarbonyl species. For instance, a new synthetic route to monosubstituted succinaldehydes allows for the facile preparation of 3-substituted pyrroles <96TL4099>. Additionally, a general method for the synthesis of 1-aminopyiroles has been devised by the condensation of commercially available 2,2,2-trichloroethyl- or 2-(tri-methylsilyl)ethylhydrazine with 1,4-dicarbonyl compounds <96JOCl 180>. A related route to such compounds involves the reaction of a-halohydrazones with p-dicarbonyl compounds <96H(43)1447>. Finally, hexamethyldisilazane (HMDS) can be utilized as the amine component in the Paal-Knorr synthesis in the presence of alumina, and this modification has been employed in the synthesis of tm azaprostacyclin analog <96S1336>. 

Succinimide is readily silylated by HMDS 2 to the N-silylated product 201, which seems, however, to be in equilibrium with the O-silylated derivative 202 a (cf the closely related reactive center in persilylated uridine 3) and reacts after 6-10 days at 24 °C with one equivalent of primary or secondary amines such as morpholine to give the crystalline colorless cyclic acylamidine 203 and HMDSO 7, even in the absence of any protective gas [33] (Scheme 4.12). The reaction is much faster on heating to 120 °C under argon. At these temperatures 201 and 202 a, and possibly also the acylamidine 203, are apparently partially O-silylated by HMDS 2 to the very sensitive 2,5-bis(trimethylsilyloxy)pyrrole 202b or to 2-tri-... 

The carboxylafion of indole into indole-3-carboxylate was observed by the purified indole-3-carboxylate decarboxylase as well as by the whole cells. For the carboxylafion reaction, temperatures over 30°C were not appropriate. The activities at 10, 20, and 30°C were about the same. The activity was maximal at pH 8.0 (Tris-HCl buffer, 100 mM). As shown in Fig. 10, the resting cells of A. nicotianae F11612 also catalyzed the carboxylafion of indole efficiently in the reaction mixture containing 20 mM indole, 3M KHCO3, 100mM potassium phosphate buffer (pH 6.0) in a tightly closed reaction vessel. By 6h, 6.81 mM indole-3-carboxylic acid accumulated in the reaction mixture with a molar conversion yield of 34%. Compared to the carhoxylation of pyrrole by pyrrole-2-carboxylate decarboxylase, the lower value compared might derive from the lower solubility of indole in the reaction mixture. 

In the tris-pentafluorophenyl analog (TFPC), in contrast to other Co corroles, aromatic amines can substitute PPh3 to form six-coordinate trivalent bis(amine) complexes.788 Bis-chlorosulfon-ation of TFPC occurs regioselectively to give the 2,17-(pyrrole)-bis-chlorosulfonated derivative fully characterized as its triphenylphosphinecobalt(III) complex.789 The amphiphilic bis-sulfonic acid was also obtained. 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

The reaction of 2-amino-2-deoxy-D-glucose (D-glucosamine) with a dicarbonyl compound was carried out for the first time by Pauly and Ludwig,91 who were trying to discover how pyrrole rings in natural products are formed. They heated free D-glucosamine and ethyl acetoacetate on a steam bath and obtained a substance in which the presence of the pyrrole ring was demonstrated by the pine-splinter test. 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

These compounds are first characterised by their magnetic behaviour. The spin-only high spin value of Fe(III) is 5.92 B.M., while a normal range for its low spin values in cubic symmetry is 2.0-2.3 B.M. [24-26]. Among the compounds listed in Table 1, these extreme cases are met by the low spin tris(l-pyrrole-dithiocarbamato)iron(III) hemikis(dichloromethane)... 

Fig. 1 Schematic drawing showing the structure of tris(A/,AT-disubstituted-dithiocarbam-ato)iron(III). Substituents R1 and R2 represent various types of alkyl groups including those being part of the ring systems morpholine, pyrrolidine or pyrrole (Table 1)... 

The difference between the Fe-S bond lengths in the high spin and low spin states is about 0.15 A, which is also in line with the Fe-S bond lengths for the low spin tris(l-pyrrole-dithiocarbamato)iron(III) hemikis(dichloro-... 

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