Thiophene synthesis - Organic Chemistry Portal

Before I continue discussing this synthesis, I’m just going to explain a little bit about nomenclature as it’ll make things easier in the long run. Most of us are probably familiar with the structure of porphyrins. Counting the double bonds which are cyclically conjugated there are 9, making these 18 electron systems and therefore Huckel aromatic (i.e. 4n +2). This makes them fairly stable, which is why nature uses them for all kinds of things. It also means they prefer to be planar, although they actually distort quite easily if enough adjacent substituents are added around the ring. The four positions between the pyrrole rings are known as the meso- positions. Now, if we add a molecule of hydrogen to a porphyrin we do this different ways. If we remove one of the double bonds that isn’t part of the aromatic annulene system then we get the chlorins, one of which is the target of this campaign.

Paal–Knorr synthesis | Wiki | Everipedia

furan synthesis suggested that the thiophene was achieved by sulfurization of the furan product ...

15/07/2016 · Paal–Knorr synthesis's wiki: ..

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.

Thiophene synthesis paal knorr – …

In 2000, B. M. Trost reported a formal synthesis of the antibiotic roseophilin. Trost's route to the macrocyclic core of roseophilin, like others, relied on a Paal–Knorr Pyrrole synthesis to obtain the fused pyrrole. Heating the 1,4-diketone with ammonium acetate in methanol with camphor sulfonic acid and 4 angstrom molecular sieves gave the pyrrole with no N-substitution. This pyrrole was found to be unstable, and as such was treated with trimethylsilyl ethoxy methoxy chloride (SEM-Cl) to protecte the pyrrole prior to isolation.

of thiophenes Paal-Knorr Thiophene Synthesis Paal Thiophene Synthesis The Paal ...

Paal–Knorr Synthesis - Mechanism - Thiophene Synthesis Mechanism..

The first three steps to the D-ring were shared with those of the A-ring, comprising selective hydrolysis of the β-ester, decarboxylation of the acid obtained, and formylation of the free position. This aldehyde was then condensed with malonic acid in the presence of aniline to give the unsaturated diacid as the Knoevenagel-type product. Hydrogenation with Raney Nickel under a hydrogen atmosphere in aqueous sodium hydroxide solution reduced the double bond, and effected monodecarboxylation to give the β-propionic acid. The α-methyl group was oxidised to the carboxylic acid, employing slightly different conditions to those used in the synthesis of the C-ring. Treatment of this compound with sodium hydroxide solution then simultaneously caused decarboxylation of this acid, as well as hydrolysis and decarboxylation of the ethyl ester. The propionic acid sidechain was then esterified using diazomethane and a semi-regioselective Vilsmeier-Haack formylation then gave a mixture of regioisomeric aldehydes. These could be separated by hydrolysis of their methyl esters to give two regioisomeric acids with very different solubilities in water. Re-esterification with yet more diazomethane gave the D-ring pyrrole in 8 steps and around 16% overall yield.

Paal-Knorr Thiophene Synthesis Organic Chemistry Portal Reactions ...

Paal - Knorr synthesis of thiophene

Also reported by Knorr is a synthesis of s from 1,3-dicarbonyls and hydrazines, 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.

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Mechanism of the Paal-Knorr Reaction: The Importance …

During the optimisation of the previous step, Woodward discovered a new isomeric ring system, which he named the phlorins, where the aromaticity of the system had been disrupted by removal of one of the annulene double bonds. The first instance of this system characterised was as an intermediate in the above sequence, which although not usually isolated, could be obtained as the dihydrobromide salt by modification of the reaction conditions. Although, obviously a number of tautomers are possible for these systems, this one seemed to exist only in a single form, and was quite stable considering the general ease of gaining aromaticity. The reason for this, which is discussed at length in paper during the initial retrosynthesis, is what Woodward referred to as ‘peripheral overcrowding’. As I’ve tried to highlight in the phlorin below, the large meso propionate substituent clashes with the two ester groups on the nearby pyrroles. In tautomers where the meso carbon is sp3 hybridised then this strain is relieved as the subtituents can avoid each other to an extent. Conversely, this strain is exacerbated when this carbon is sp2 as all three substituents are forced to be coplanar, and this effect disfavours isomers where this the case. It is worth noting that although these compounds are stable enough to isolate and characterise, oxidation can still be effected using fairly mild oxidants such as the quinones DDQ and chloranil, or even molecular oxygen.

ammonium acetate or Lawesson's reagent by the Paal-Knorr synthesis…

This wide array of interesting properties has inspired the development of a variety of procedures for the preparation of differently substituted pyrroles. Methods of synthesis include the classical Knorr, Paal-Knorr and Hanstzch strategies, transition-metal-catalyzed couplings, 1,3-dipolar cycloadditions procedures and multicomponent protocols. 1d,3 On the other hand, methods for the construction of 2-(2′-thienyl)pyrroles remain limited. 4