Pyrroles from furans

Cation exchange resin Pyrroles from furans... 

From the preceding examples it can be seen that oxidants and electrophilic reagents attack pyrroles and furans at positions 2 and 5 in the case of indoles the common point of attack is position 3. Thus autoxidation of indoles e.g. 99) gives 3-hydroperoxy-3H-indoles (e.g. 100). Lead tetraacetate similarly reacts at the 3-position to give a 3-acetoxy-3H-indole. Ozone and other oxidants have been used to cleave the 2,3-bond in indoles (Scheme 30) (81BCJ2369). 

Chemistry of conjugated heterocycles built from furan pyrrole, or thiophene ring fused with bicyclic (norbomadiene, bomene, or azanorbomene) skeletons 98YGK192. 

Scheme 28 Synthesis of pyrrole and furan derivatives 134 from the 1-methoxyethyli-denechromium complex 6a and enyneketimines or -ketones 131 [92,93]. For further details see Table 6...

The nomenclature and numbering used above are recommended by lUPAC (1998PAC143), and they can be further applied to the other cyclic systems with one or more heteroatoms on the heteropine ring using the order of preference rules. Thus, fusion of pyrrole (54), furan (71) or thiophene (78) with azepine (43), oxepine (67) or thiepine (78) results in chemical names in which the parent heterocycle has the lowest preference number and is cited last in the name (preference numbers from Appendix II (1998PAC143) are in brackets). Explanation of the fusion descriptors can be found in the lUPAC recommendations (1998PAC143) and were exemplified in CHEC-I (1984CHEC-1(1)7). 

Oxyiminium cations formed from iV,0-diaIkyhydroxylamines and formaldehyde are sufficiently reactive for Mannich reactions with activated arenes. Mannich reactions of oxyiminium cations with indoles (e.g. 74, equation 48) " as well as pyrroles and furans but not phenol and thiophene have been reported. 

Thiophene is present in the benzene fraction from the distillation of coal tar. As with pyrrole and furan, the same type of resonance forms contribute to its overall molecular constitution, and the compound is aromatic in character. There is a difference between thiophene and furan, however, because sulfur is less electronegative than oxygen. Thus, the chemistry of thiophene tends to be closer to that of pyrrole than to that of furan. For example, thiophene does not enter easily into [4 + 2] cycloaddition reactions and quite severe conditions, high pressure (15 bar) and a temperature of 100 C, are necessary in order to force a cycloaddition between it and maleic anhydride. 

Positive sign denotes a downfield shift from furan and methyl pyrrole-2-carboxylate, respectively. Chemical shifts for furan are 143.6 (C-2), 110.4 (C-3) <1975CS211>, and for methyl pyrrole-2-carboxylate 122.0 (C-2), 115.1 (C-3) <1974JP21004>. 

Note that dipoles are generated in pyrrole and furan because of delocalization of electrons from the heteroatoms. 

The five-membered aromatic heterocycles pyrrole (5), furan (6) and thiophene (7) are formally derived from cyclopentadienyl anion by replacement of one CH group with NH, O or S, each of which can contribute two p-electrons to the aromatic ir-electron sextet. Heteroatoms of this type have in classical structures only single bonds and are called pyrrole-like . Other five-membered aromatic heterocycles are derived from compounds (5), (6) and (7) by further replacement of CH groups with N, 0+ or S+. 

Indolizines with a saturated six-membered ring may be obtained from pyrrole or furan derivatives.225,226 The reaction of 3,4-dimethylpyrryl-magnesium bromide with y-chlorobutyronitrile followed by dilute acid gave 5,6,7,8-tetrahydro-l,2-dimethyl-5-oxoindolizine. 5,6,7,8-Tetrahy-droindolizine can be obtained by the cyclodehydration of 3-(2-furyl)-propylamine over alumina at 400°C. The same product is obtained by the treatment of 3-(2-pyrryl)propyl cyanide with hydrogen chloride in the presence of boron trifluoride etherate catalyst, followed by Wolff-Kishner reduction of the intermediate ketone. 

Double cyclopropanation of furans and pyrroles with aryl diazoacetates catalysed by Rh2(S-DOSP)4 have been reported to occur with opposite stereochemistry depending on the nature of the heterocycle.55 Better yields and ees are achieved for tricycles (69) derived from furan than for (68) derived from more bulky pyrroles. Monocyclo- propanation (with high yields and ees) is achieved on the furan ring of benzofuran, whereas double cyclopropanation of the indole is observed. 

There is increasing evidence that the interaction of lipids with the Maillard reaction is relevant to the generation of flavor in many cooked foods. For instance, the removal of lipids from coconut has been shown to cause flavor changes in the roast material (12). Uncooked coconut contained significant amounts of lactones as the main aroma components on roasting pyrazines, pyrroles and furans were also found in the aroma volatiles which added a strong nut-like aroma to the sweet aroma of the unroasted coconut. When ground coconut was defatted and then roasted, the sweet aroma due to lactones disappeared and the product possessed a burnt, nut-like aroma. A marked increase in the number and amount of Maillard reaction products, in particular pyrazines, was found. 

The relative reactivities of all four unsubstituted rings have been subsequently determined in another electrophilic substitution trifluoroacetylation by trifluoroacetic anhydride in dichloroeth-ane.142 143 The relative rates, obtained by a competitive procedure, are in good agreement with the bromination data (Table V) and confirm, in particular, the big jump in reactivity from furan to pyrrole. The great reactivity of pyrrole cannot be ascribed to a reaction involving the anion C4H4N, since V-methylpyrrole is still more reactive than pyrrole by a factor of about 2. 

Oxazole (22), thiazole (23), and imidazole (24) are formally derived from furan, thiophene, and pyrrole by replacement of a /J-CH group... 

Oxazole, imidazole, and thiazole can be formally derived from furan, pyrrole, and thiophene respectively by replacement of a CH group by a nitrogen atom at the 3 position. The presence of this pyridine-like nitrogen deactivates the 1,3-azoles towards electrophilic attack and increases their susceptibility towards nucleophilic attack (see later). These 1,3-azoles can be viewed as hybrids between furan, pyrrole, or thiophene, and pyridine. 

Nevertheless, this collection of heterocycles does share certain characteristics. The trend we have seen of decreasing tendency towards electrophilic substitution on going from furan, pyrrole, and thiophene to the azoles is continued into these series. The presence of additional pyridine-like nitrogen atoms renders these systems particularly electron-deficient, and electrophilic substitution is of little importance. 

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