Paal–Knorr synthesis | Wiki | Everipedia
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.
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.