3-Hydroxypyrroles and 1H-pyrrol-3(2H)-ones. Part 2. Scope and limitations of the synthesis of pyrrol-3-ones by pyrolysis of aminomethylene Meldrum's acid derivatives

Formation of isomeric pyrrolones by flash vacuum pyrolysis of bisaminomethylene derivatives of Meldrum’s acid

“…However, the major initial breakdown peak observed in all cases (base peak for 7a and 7c) is formed by loss of fragment(s) totaling 76 Da from the molecular ions. This may be owing to cleavage of C 3 H 6 O and H 2 O (as we have previously confirmed in the special case of N-amino groups with saturated cyclic substituents) 9 but the nature of the species formed requires further investigation. The NMR spectra of 7a-7c are in accord with the proposed structures.…”

“…2:1 (after statistical correction). 9 In addition, a concerted hydrogentransfer-cyclisation process from the methyleneketene 3 can be excluded because the configuration of an asymmetric center at the site of hydrogen transfer (e.g., Scheme 1, R 1 = Pr i , R 2 = Me, R 3 = Ph) is partially lost in the final pyrrolone. 10 It has been proposed that it is the 1,5-dipolar species 4 which undergoes the final electrocyclic ring closure to give the products 5 in both the nitrogen and the sulfur series, [9][10][11] but why are such intermediates not observable spectroscopically?…”

Preparation and pyrolysis of some N-protected derivatives of aminomethylene Meldrum’s acid

“…1,2 Because of their electron rich nature and sensitivity to oxidation, 3-hydroxypyrroles are often difficult to obtain by other means. However, this route is not directly applicable to the preparation of N-unsubstituted hydroxypyrroles 2 (R 1 = H), since the pyrolysis takes we hoped would lead to N-protected 3-hydroxypyrroles.…”

“…Hydrogenolysis of N-benzyl groups is a common means of deprotection which has been used in the alkoxypyrrole series. 13 Because pyrolysis of N-alkyl-Nbenzylaminomethylene Meldrum's acid derivatives always leads to N-alkyl-2-phenyl-3-hydroxypyrroles via hydrogen transfer from the benzyl CH 2 group, 1 we hoped that the dimethylbenzyl group would provide required protection (Scheme 4). We therefore briefly investigated the temperature profile of the pyrolyses of Nmethylbenzylamine 26 (which gives bibenzyl), N-α-dimethylbenzylamine 27 (which gives styrene) and N,α,α-trimethylbenzylamine 23 (which gives α-methylstyrene) (Figure 1, series 3, 2 and 1 respectively).…”

“…The N-benzyl substituent was chosen because of the high reactivity of benzyl-type hydrogen atoms to the transfer-cyclisation process, 1 and so the known N-benzylhydrazine 12 9 was synthesised and reacted with MMMA 3 to give the pyrolysis precursor 10 in 44% …”