Synthesis Knorr

In the Knorr route, 1,3-dicarbonyl compounds react with hydrazines under ring closure to pyrazoles [20]. 

The following library consisting of seven (A1-A7) 1,3-dicarbonyl compounds and three hydrazines (B1-B3) was synthesized. 

The results obtained were compared for consistency to single-reaction processing on the same chip. N o cross-contamination was found during preparation of the library [20]. The products, by-products, or the hydrazine in excess were not intermixed. 

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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 ... 

The usefulness of the Knorr synthesis arises from the fact that 1,3-dioxo compounds and a-aminoketones are much more easily accessible in large quantities than rational 1,4-difunctional precursors. Such practical syntheses are known for several important hetero-cycles. They are usually limited to certain substitution patterns of the target molecules. 

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. 

The Knorr synthesis is not particularly sensitive to the nature of R and ie, they may be alkyl, acyl, aryl, or carbalkoxy without significantly affecting the yield. Similarly, good yields are obtained if R and R are acyl or carbalkoxy, but poor yields are obtained if they are alkyl or aryl. 

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. 

Paal-Knorr synthesis, 4, 118, 329 Pariser-Parr-Pople approach, 4, 157 PE spectroscopy, 4, 24, 188-189 photoaddition reactions with aliphatic aldehydes and ketones, 4, 232 photochemical reactions, 4, 67, 201-205 with aliphatic carbonyl compounds, 4, 268 with dimethyl acetylenedicarboxylate, 4, 268 Piloty synthesis, 4, 345 Piloty-Robinson synthesis, 4, 110-111 polymers, 273-274, 295, 301, 302 applications, 4, 376 polymethylation, 4, 224 N-protected, 4, 238 palladation, 4, 83 protonation, 4, 46, 47, 206 pyridazine synthesis from, 3, 52 pyridine complexes NMR, 4, 165... 

Quinolin-2-one, 3-cyano-4-hydroxy-synthesis, 2, 428 Quinolin-2-one, 3,4-dialkyl-Knorr synthesis, 2, 425 Quinolin-2-one, dihydro-Camps synthesis, 2, 418 synthesis, 2, 402 from benzazepinones, 2, 506 from indanone oxime, 2, 487 from indanones, 2, 488 by intramolecular Friedel-Crafts reactions, 2, 421... 

Cyclizations such as that which underlies the Knorr synthesis have also been successfully used in Robinson annelation sequences [72] (equation 12)... 

The Knorr synthesis is a venerable process that has found a number of useful synthetic... 

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>. 

Dual Alkyliminodeoxo Bisubstitution and Ring Closure - Knorr Synthesis... 

Drivers for Performing Knorr Synthesis in Micro Reactors... 

The Knorr synthesis was chosen as an example to demonstrate that with an automated micro-reactor system a further step was made over existing parallel micro flow processing techniques, providing a 2 x 2 library in a chip micro reactor [20]. The new approach was designed for much higher diversity, aiming at a 7 x 32 library. 

Hence the investigations made so far were aimed more at showing the capability of an automated micro-reactor system, using the Knorr synthesis as a model reaction however, to a certain extent, information on this synthesis itself was also gained (see Section 4.9.6.5) [20]. The Knorr synthesis of pyrazoles chosen is of industrial interest since by this route compounds with a wide range of biological activity can be produced. 

Finally, Scharf and Wolters report a method said to be superior to both the Paal-Knorr synthesis (starting materials more easily accessible) and the Feist-Benary synthesis (freer choice for 3-substituent). Thermal rearrangement-elimination by alkylated dioxolanes at 230 C gives alkyl substituted furans. Yields can be nearly quantitive since the only serious by-products also give the furans under proton-catalyzed thermolysis (Scheme 25).124 Photochemical methods are outlined in Section VII. 

Ferreira developed a novel method for the preparation of masked 1,4-dicarbonyl derivatives for utilization in the Paal-Knorr synthesis of pyrroles <00SC3215>. In this process, the reaction between diazocompound 3 and n-butyl vinyl ether using dirhodium tetraacetate as catalyst provides dihydrofurans 4 which are easily converted into substituted... 

Conrad-Limpach-Knorr synthesis, of quinolines, 21 189 Conrad recycling process, 21 455 Conradson carbon test method, 11 705, 721 Consensus materials standards, 15 743 Consent decree protocols, in the United States, 11 692-694 Consent decrees, 11 689-690 Consequence analysis, 21 860-861 Consequence modeling, 13 165-166 Conservation applications, high performance fibers in, 13 398 Conservation of energy, 21 290 Conservation of mass, 11 737, 738-739 Conservation, of resources, 24 164-167 Conservation scientists, 11 398-399 Consistent force field, 16 744 Consolidants, in fine art examination/ conservation, 11 410... 

From Fischer synthesis. b From Koenigs-Knorr synthesis. 

Knoevenagel reaction org chem The condensation of aldehydes with compounds containing an activated methylene (=Cff2) group. ka ne va.nag al re.ak shan ) Knorr synthesis orgchem Acondensation reaction carried out In either glacial acetic acid or an aqueous alkali in which an a-aminoketone combines with an a-carbonyl compound to form a pyrrole possibly the most versatile pyrrole synthesis. nor, sin-th3-s3s ... 

Paal-Knorr synthesis orgchem A method of converting a 1,4-dicarbonyl compound by cyclization with ammonia or a primary amine to a pyrrole. pol ko nor sin-... 

Quinolones are obtained in the Conrad-Limpach-Knorr synthesis, which is subject to either kinetic or thermodynamic control, when aniline is reacted with a 3-keto ester (Scheme 3.11a). At room temperature the more reactive keto group combines with the aniline nitrogen atom, leading to an enamino ester the kinetic product. Cyclization of this product to a 4-quinolone requires heating at 250 C. 

There are two principal routes to pyrroles. One is called the Paal-Knorr synthesis, in which pyrroles are formed by the interaction of 1,4-dicarbonyl compounds and ammonia. No intermediates have ever been isolated, so the mechanism shown in Scheme 6.13 is speculative. 

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