Knorr pyrrole synthesis 6a The Paal-Knorr pyrrole method is useful for making pyrrole rings as long as the starting 1,4-dicarbonyl compound is readily available. For example: Eto,C, CHs EtO.C, CH3 ° CH3 TL = H3C: CO;Et = mo NOH H3C— XC OLEt 3 os N 0 6 Et0,c 0 + NH3 An alternative method, known simply as the Knorr pyrrole synthesis, involves the reaction of an a-aminoketone with another ketone. Et0.C, CH. Et0,€, cH; E1024 CH; H > ic \ CO; ne 3 COzEt bo H3C COZEt Na 2 This retrosynthetic analysis £1026 CH3 outlines the rationale for the method. Note the special —_— arrows indicating this is H3c ‘CO2Et "paper chemistry" 0 NH,Knorr pyrrole synthesis: mechanism 6b Looking the example above we note that the oamino-f-ketoester and i-ketoester have the same carbon skeleton. In this case the o-amino-f-ketoester can be made in situ with a second mole of the B-ketoester to yield the pyrrole directly. Rt 0. pe R' =CO,Et > pi R= CHS R t proton X ‘exchange H RA HOUR? RL 0, UR? RL) oR? RK og UR? L I L XL el mr i 4 R27 “n~ Rr! R27 Sn~ “Rt R27 Sn~ “Rt N* ~R H H H HQ, H | Rt R? Rt R? Ht Re R? = — qo R?NO”>R! R? ‘ Rt RN SR! R? (3 R! N NO N H HThe Knorr pyrrole synthesis: "unsymmetrical" pyrroles 7a The Knorr pyrrole synthesis does not need to be done in “one pot". The amino ketone component can be made separately, then condensed with another carbonyl containing compound, so giving access to a wider range of pyrroles Synthesis of a-aminoketones 9 9 9 Zn HCI, NaNO, CO,Et _AcOH CO,Et A cout ee Bifunctional Chemistry notes, slide 13a Non NH, __ Bae we _NaNs Hai Pac Chemistry notes, slide 11a Rt rR Oo: + eo R27 So HN’The Knorr pyrrole synthesis: examples Examples of pyrroles made using the Knorr method Eto,c 1] a HN C4Hy EtO,C. A, =< + —> 0 HN Ph Ph + ? —> Ph H~ No HN 7b How would you make this pyrrole? Oo [ \ xz