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A versatile synthesis of cyclic dipeptides using the stepwise construction of the piperazine‐2,5‐dione ring from simple precursors: synthetic sequence and the structure of a representative product, (3 RS )‐4‐(2‐allyl‐3,5‐dimethylphenyl)‐1‐benzyl‐3‐phenylpiperazine‐2,5‐dione
Author(s) -
Acosta Quintero Lina M.,
Palma Alirio,
Cobo Justo,
Glidewell Christopher
Publication year - 2018
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229618000037
Subject(s) - piperazine , ring (chemistry) , chemistry , molecule , benzylamine , hydrogen bond , yield (engineering) , stereochemistry , medicinal chemistry , organic chemistry , materials science , metallurgy
A versatile synthesis of multiply substituted cyclic dipeptides has been designed, based on the stepwise construction of the piperazine‐2,5‐dione ring using molecular fragments from four different precursor molecules. Starting from substituted 2‐allylanilines, reaction with methyl 2‐bromo‐2‐phenylacetate yields the corresponding methyl 2‐(2‐allylanilino)‐2‐phenylacetates, which react with haloacetyl chlorides to give methyl 2‐[ N ‐(2‐allylphenyl)‐2‐haloacetamido]‐2‐phenylacetates, which then undergo ring closure with benzylamine to yield the corresponding cyclic dipeptides of type 4‐(2‐allylphenyl)‐1‐benzyl‐3‐phenylpiperazine‐2,5‐dione. (3 RS )‐4‐(2‐Allyl‐3,5‐dimethylphenyl)‐1‐benzyl‐3‐phenylpiperazine‐2,5‐dione, C 28 H 28 N 2 O 2 , (III d ), crystallizes with Z ′ = 2 in the space group P 2 1 / c ; the allyl groups in the two independent molecules adopt different conformations and, in one of them, the allyl group is disordered over two sets of atomic sites having occupancies of 0.534 (4) and 0.466 (4). In both molecules, the piperazine‐2,5‐dione ring adopts a boat conformation, with the 3‐phenyl ring in a quasi‐axial site. The molecules of (III d ) are linked into a three‐dimensional framework structure by a combination of three C—H…O hydrogen bonds and three C—H…π(arene) hydrogen bonds. Comparisons are made with some related structures.