Knorr pyrrole synthesis - Wikipedia
Several 1,4-dicarbonyl surrogates can be used in place of a 1,4-dicarbonyl. While these substitutes have different structures from a 1,4-dicarbonyl, their reactions proceed via mechanisms very similar to that of the Paal-Knorr.
Mechanism of the Paal-Knorr Furan Synthesis
In 1982, H. Hart reported a synthesis of a macrocycle containing fused furan rings using a Paal–Knorr furan synthesis. Refluxing -toluene sulfonic acid in benzene was found to dehydrate the 1,4-diketones to their respective furans to achieve the challenging macrocyclic fused furans.
Also reported by Knorr is a synthesis of s from 1,3-dicarbonyls and , hydrazides, or semibicarbazides. This synthesis occurs via a condensation mechanism similar to the Paal-Knorr, however if a substituted hydrazine is used, it results in a mixture of regioisomers wherethe substituted heteroatom is either next to the R1 substituent or the R3 substituent.
Hantzsch pyrrole synthesis - Wikipedia
Meanwhile, Johnson had extended the Fischer-Fink synthesis byreacting 2-oximinoacetoacetate esters (ethyl, benzyl, ortertiary-butyl), with 3-alkyl substituted 2,4-pentanediones. Others extended the Kleinspehn synthesis by the use ofunsymmetrical beta-diketones (such as 3-alkyl substituted2,4-hexanediones), which preferentially reacted initially at theless hindered acetyl group and afforded the corresponding5-methylpyrrole-2-carboxylate esters. N,N-Dialkyl2-oximinoacetoacetamides also were found to give pyrroles whenreacted under Knorr conditions with3-substituted-2,4-pentanediones, in yields comparable to thecorresponding esters (around 45%). However, when unsymmetricaldiketones were used, it was found that the acetyl group from theacetoacetamide was retained in the product, and one of the acylgroups from the diketone had been lost. Thissame mechanism occurs to a minor extent in the acetoacetate estersystems, and had previously been detected radiochemically byHarbuck and Rapoport. Mostof the above-described syntheses have application in the synthesisof porphyrins, bile pigments, and dipyrrins.
The Hantzsch Pyrrole Synthesis, ..
Another variation has been the introduction of microwave radiation to enhance the Paal–Knorr. Traditional Paal–Knorr conditions involved prolonged heating of strong acids to drive dehydration which occurred over a period of several hours. Microwave-assisted Paal–Knorr reactions have been demonstrated to occur on time scales measured in minutes and in open flasks at room temperature.
such as the Knorr Pyrrole Synthesis and Paal-Knorr Synthesis
1,4-diol-2-yne systems have also been used to do Paal–Knorr chemistry. Using palladium, a 1,4-diol-2-yne can be isomerized to the corresponding 1,4-diketone and then dehydrated to the corresponding furan using a dehydration agent.
Knorr pyrrole synthesis - WikiVisually
Fischer and Fink found that Zanetti's synthesis from2,4-pentanedione and ethyl 2-oximinoacetoacetate gave ethyl3,5-dimethylpyrrole-2-carboxylate as a trace byproduct. Similarly,3-ketobutyraldehyde diethyl acetal led to the formation of ethyl5-methylpyrrole-2-carboxylate. Both of these products resulted fromthe loss of the acetyl group from the inferred ethyl2-aminoacetoacetate intermediate. An important product of theFischer-Fink synthesis was ethyl 4,5-dimethylpyrrole-2-carboxylate,made from ethyl 2-oximinoacetoacetate and 2-methyl-3-oxobutanal, inturn made by the of with . ,