Knorr Pyrrole Synthesis Research Articles

Elegant synthesis of novel pyrroles and dipyrrylmethane of biosynthetic importance

Ethyl 4-ethoxycarbonylmethyl-3,5-dimethylpyrrole-2-carboxylate (1) has been synthesized by extension and modification of Knorr pyrrole synthesis. Its acetoxymethyl derivative (2) has also been synthesized. Diethyl 3,3'-bis(ethoxycarbonylmethyl)-4,4'-dimethyl-2,2'-dipyrrylmethane-5,5'-dicarboxylate has been synthesized by self-condensation of 2.

Microreaction Technology as a Novel Approach to Drug Design, Process Development and Reliability

This paper focuses on the application of microreaction technology in the life science industry. Certain features of microreaction technology, for example, mixing, heat transfer, and residence time distribution, are discussed. Important advantages such as high operational safety and the possibility to transfer the experimental results directly from laboratory to the production of pilot-plant scales are mentioned. Potential application fields in the drug discovery and development processes, from research to production, by including chemical synthesis of different targets in the case of the quinoline acid derivative (ciprofloxacin) and the Paal−Knorr pyrrole synthesis are presented.

Elucidation of the mechanism of pyrrole formation during thermal degradation of 13C-labeled l-serines

Pyrolysis of [13C-1], [13C-2] and [13C-3]-labelled l-serines generated mono-substituted methyl and ethyl derivatives of pyrroles and pyrazines among other compounds. Analyses of label incorporation into the pyrroles have indicated their formation through aldol condensation of acetaldehyde with different α-aminocarbonyl compounds followed by cyclization and loss of water (Knorr pyrrole synthesis). Comparison of the label incorporation patterns of the α-aminocarbonyls involved in the formation of methyl and ethyl-substituted pyrroles with that of similarly substituted pyrazines, revealed their common origin. In addition, α-aminocarbonyls involved in the formation of 2- and 3-substituted pyrroles had identical label distribution patterns, indicating their formation through the same carbonyl precursors. Furthermore, the major pathway (55%) leading to the formation of the α-aminocarbonyl precursors of methyl-substituted pyrroles involved aldol addition of formaldehyde to glycolaldehyde, whereas the only pathway leading to the formation of the α-aminocarbonyl precursors of ethyl-substituted pyrroles involved the interaction of alanine — formed in situ — with glycolaldehyde.

2-Hetaryl-Substituted Bis(indenyl)zirconium Complexes as Catalyst Precursors for Elastomeric Polypropylene Formation

2-Indanone was treated with 2-lithio-5-methylfuran and the addition product dehydrated to yield the 2-(5‘-methyl-2‘-furyl)-substituted indene 2. Deprotonation with n-butyllithium followed by transmetalation to zirconium gave the bis(2-furylindenyl)ZrCl2 complex 4a. Subsequent reaction with methyllithium yielded the corresponding bis(2-furylindenyl)ZrMe2 system 6a. The related bis[2-(5‘-methyl-2‘-furyl)indenyl]hafnium complexes (5a, 7a) and the bis[2-(5‘-methyl-2‘-thienyl)indenyl]zirconium and -hafnium complexes 4b−6b were synthesized analogously. In the crystal the bis(2-furylindenyl)ZrCl2 (4a) and -HfCl2 (5a) complexes exhibit meso-like metallocene conformations, as shown by X-ray diffraction. In contrast, the bis(2-furylindenyl)ZrMe2 system (6a) shows a chiral, close to C2-symmetric rac-like metallocene conformation in the solid state. Hydrolysis of 2-(5‘-methyl-2‘-furyl)indene (2a) followed by Paal−Knorr pyrrole synthesis of the resulting 1,4-diketone 8 with methylamine gave (5‘-methyl-2‘-N-methylpyrro...

Versatility of Weinreb amides in the Knorr pyrrole synthesis

N-Methoxy- N-methyl-α-enaminocarboxamides were prepared starting from enamines and Weinreb α-aminoamides. Their reaction with oganometallic compounds and subsequent cyclization constitute a versatile alternative in the Knorr pyrrole synthesis.

Formal synthesis of roseophilin

A thirteen step route to the tricyclic ketopyrrole core of roseophilin is presented in which the final step consists of a Paal–Knorr pyrrole synthesis that proceeds with in situ oxidation.

A new variant of Knorr's pyrrole synthesis

AbstractThe reaction between ethyl 3‐bromopyruvate and p‐substituted anilines was found to involve the unexpected participation of acetone (solvent) forming N‐aryl‐5‐methyl‐pyrrole‐3‐carboxylates. The influence of p‐substituents of aniline and the feasibility with other ketones were studied. N‐aryl‐indole‐3‐carboxylate (17) was synthesized successfully with this method. The unique character of p‐methoxy‐aniline in this reaction was discussed.

ChemInform Abstract: α‐Amino Ketones from Amino Acids as Precursors for the Knorr Pyrrole Synthesis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A-Amino Ketones from Amino Acids as Precursors for the Knorr Pyrrole Synthesis

A useful and versatile modification of the Knorr pyrrole synthesis is described. Key α-amino ketone intermediates for the Knorr condensation were readily prepared from the N-methoxy-N-methylamides of amino acids and condensed with 1,3-dicarbonyl compounds to afford tetrasubstituted pyrroles in good yields

On the mechanism of pyrrole formation in the knorr pyrrole synthesis and by porphobilinogen synthase

Attempts to synthesise a derivative of N-vinylaminoethanal either by oxidation of the corresponding alcohol or by hydrolysis of the corresponding dithioacetal were unsuccessful, but such derivatives were characterised by 1H and 13C NMR spectroscopy of reactions between ethyl 2-aminoacetoacetate and an excess of ethyl acetoacetate, leading to diethyl 2,4-dimethylpyrrole-3,5-dicarboxylate.

4,5,8,9‐tetrahydro‐8‐methyl‐9‐oxothieno[3′,2′:5,6]cyclohepta[1,2‐b]‐ pyrrole‐7‐acetic acid. A new anti‐inflammatory/analgesic agent

AbstractThe synthesis of the thienocyclohepta[1, 2‐b]pyrrole acid 1 from the morpholide 3 is reported. This novel morpholide was prepared by regiospecific alkylation of the dianion of 4‐(1, 3‐dioxobutyl)morpholine with 3‐bromomethylthiophene. Subsequent Knorr pyrrole synthesis led to the morpholide 8b which was converted to the desired tricyclic ring system under Vilsmeier conditions. An alternative route involving Friedel‐Crafts cyclisation was used to prepare the related benzocycloheptapyrrole 2.

Synthesis of a 2,3'-bipyrrole. Denitrosation in the Knorr pyrrole synthesis

Synthesis of a 2,3'-bipyrrole. Denitrosation in the Knorr pyrrole synthesis

Total Synthesis of Pyrrolnitrin. I. Synthesis of 3-Arylpyrrole Derivatives by Knorr's Condensation

Alkyl 3-aryl-5-methyl-4-pyrrolecarboxylate (IIIa-j) and alkyl 2, 5-dimethyl-3-aryl-4-pyrrolecarboxylate (IIIk-m), two kinds of key intermediates for synthesizing pyrrolnitrin (I), were obtained from 2-aminoacetophenones (IV) and alkyl acetoacetate by Knorr's pyrrole synthesis. The mechanism of the pyrrole ringclosure of the above compounds was proposed since alkyl 3-substituted benzoylmethylaminocrotonates (VIII) could be isolated as intermediates presumably because of their difficult cyclization to the corresponding pyrroles ; for which the infrared spectra of nitro and carbonyl group of VIII were discussed.

An extension of Knorr's pyrrole synthesis

An extension of Knorr's pyrrole synthesis