Pyrroles 3- formyl

Pyrrole, 4-ethynyl-2-formyl-3-methyl-synthesis, 4, 222 Pyrrole, formyl-oxidation, 4, 289 reactions, 4, 292 with sulfoxides, 4, 293 synthesis, 4, 223, 274, 287 Pyrrole, 1-formyl-barrier to rotation, 4, 193 Pyrrole, 2-formyl-benzoylation, 4, 220 conformation, 2, 107 4, 193 diacetoxythallium derivative iodination, 4, 216 dipole moment, 4, 194 ketals, 4, 290 protonation, 4, 47 reactions... 

Vilsmeier formylation of the thienylpyrroles 49 gives only the pyrrole-formylated products (Equation 14) <2006T3493>. The formyl group could be introduced on the thiophene ring by lithiation and subsequent treatment with DMF. 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

On treatment with Vilsmeier salts, V-alkylpyrroles formylate in the expected 2-position unless the alkyl group is bulky, in which case formylation at the 3-position is preferred. The 2-substituted pyrroles tend to formylate at the 5-position, and 3-substituted pyrroles formylate at the 2- and 5-position with low regioselectivity. 

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

Conjugated dipyrrolic pigments, the dipyrromethenes, are synthesized by add-catalyzed condensation of an a-formyl pyrrole and an a-unsubstituted pyrrole. They are readily protonated and deprotonated and are difficult to purify by chromatography. 

The pyridine-like nitrogen of the 2H-pyrrol-2-yiidene unit tends to withdraw electrons from the conjugated system and deactivates it in reactions with electrophiles. The add-catalyzed condensations described above for pyrroles and dipyrromethanes therefore do not occur with dipyrromethenes. Vilsmeier formylation, for example, is only successful with pyrroles and dipyrromethanes but not with dipyrromethenes. 

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. 

Viaylpyrroles and 3-vinylpyrroles can be prepared by the base-catalyzed condensation of the corresponding formyl pyrroles with activated... 

Alkyl substituents. The steric effect of 1-alkyl substituents in the pyrrole series has been demonstrated in, for example, Vilsmeier formylation reactions. Thus as the bulk of the alkyl substituent on nitrogen is increased e.g. from Me to Bu ) so does the proportion of /3 substitution (70JCS(C)2573). A similar trend has been observed in a series of experiments on the trifiuoroacetylation of A-alkylpyrroles with trifluoroacetic anhydride (80JCR(S)42). 

Frontier orbital theory predicts that electrophilic substitution of pyrroles with soft electrophiles will be frontier controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles will be charge controlled and occur at the 3-position. These predictions may be illustrated by the substitution behaviour of 1-benzenesulfonylpyr-role. Nitration and Friedel-Crafts acylation of this substrate occurs at the 3-position, whereas the softer electrophiles generated in the Mannich reaction (R2N=CH2), in formylation under Vilsmeier conditions (R2N=CHC1) or in formylation with dichloromethyl methyl ether and aluminum chloride (MeO=CHCl) effect substitution mainly in the 2-position (81TL4899, 81TL4901). Formylation of 2-methoxycarbonyl-l-methylpyrrole with... 

Vilsmeier-Haack formylation, 4, 222 Pyrrole, 3-acetyl-oxidation, 4, 289 protodeaeetylation, 4, 208 synthesis, 4, 218... 

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... 

Pyrrole, l-(2-acylaminophenyl)-intramolecular aeylation, 4, 223 Pyrrole, 3-acyl-2-ehloromethyl-reactions, 4, 274 Pyrrole, 3-acyl-2-formyl-reactions... 

N-alkylation, 4, 236 Pyrrole, 2-formyl-3,4-diiodo-synthesis, 4, 216 Pyrrole, 2-formyl-1-methyl-conformation, 4, 193 Pyrrole, 2-formyl-5-nitro-conformation, 4, 193 Pyrrole, furyl-rotamers, 4, 546 Pyrrole, 2-(2-furyl)-conformation, 4, 32 Pyrrole, 2-halo-reactions, 4, 78 Pyrrole, 3-halo-reactions, 4, 78 Pyrrole, 2-halomethyl-nucleophilic substitution, 4, 274 reactions, 4, 275 Pyrrole, hydroxy-synthesis, 4, 97 Pyrrole, 1-hydroxy-cycloaddition reactions, 4, 303 deoxygenation, 4, 304 synthesis, 4, 126, 363 tautomerism, 4, 35, 197 Pyrrole, 2-hydroxy-reactions, 4, 76 tautomerism, 4, 36, 198... 

Pyrrole, 2-methyoxycarbonyl-1 -methyl-formylation, 4, 45 Pyrrole, nitro-rearrangement, 4, 297 Pyrrole, 2-nitro-nitration, 4, 211 photolysis, 4, 203 radical methylation, 4, 260 synthesis, 4, 210, 362 Pyrrole, 3-nitro- N NMR, 4, 13 nitration, 4, 211 synthesis, 4, 49, 210, 362 Pyrrole, nitroso-rearrangement, 4, 297 Pyrrole, 2-nitroso-reactions... 

Pyrrole-2-carboxylic acid, 4,5-dimethyl-ethyl ester formylation, 4, 217 Pyrrole-2-carboxylic acid, 3-hydroxy-... 

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 applicability of the Reimer-Tiemann reaction is limited to the formylation of phenols and certain reactive heterocycles like pyrroles and indoles. Yields are usually below 50%. In contrast to other formylation procedures, the Reimer-Tiemann reaction is ort/zo-selective it is therefore related to the Kolb e-Schmitt reaction. 

With respect to aromatic substrates, the Vilsmeier formylation reaction works well with electron-rich derivatives like phenols, aromatic amines and aromatic heterocycles like furans, pyrroles and indoles. However various alkenes are also formylated under Vilsmeier conditions. For example the substituted hexatriene 6 is converted to the terminal hexatrienyl aldehyde 7 in 70% yield ... 

Finally, the isoporphyrins with a nitrogen atom inverted from the inner core into a /5-pyrrolic position can be prepared by classical porphyrin synthetic routes when the pyrrolelinking CH2X or formyl group is attached to the /J-position of the pyrrole subunit instead of the a-position of the pyrrole as in the synthesis of regular porphyrins. 

Acid-induced cyclization of the appropriate (hydroxypropenyl)pyrroles 30, which can be easily derived from a-unsubstituted pyrroles by vinylogous Vilsmeier reaction followed by reduction of the formyl function, yields the corresponding expanded porphyrinogens 31. The... 

Elektronenreiche Carboxy-N-heteroarene erleichtern ebenfalls die Hydrogenolyse (anwesende Alkoxycarbonyl- bzw. Formyl- oder Acyl-Gruppen werden mitreduziert). Pyrrol-carbonsauren werden z. B. durch Lithiumalanat in Diathylather oder THF zu den entsprechenden Methyl-pyrrolen reduziert4 s z, B.4 ... 

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