112142-53-7Relevant academic research and scientific papers
Synthesis and crystal structure of 3,3,6,6-tetramethylmorpholine-2,5-dione, and its 5-monothioxo and 2,5-dithioxo derivatives
Mawad, Nasser,Ghorbani-Salman Pour, Fatemeh,Linden, Anthony,Heimgartner, Heinz
, p. 2326 - 2346 (2011/02/18)
The synthesis of 3,3-dimethylmorpholine-2,5-diones 4a was achieved conveniently via the 'direct amide cyclization' of the linear precursors of type 3, which were prepared by coupling of 2,2-dimethyl-2H-azirin-3-amines 2 with 2-hydroxyalkanoic acids 1. Thionation of 4a with Lawesson's reagent yielded the corresponding 5-thioxomorpholin-2-ones 10 and morpholine-2,5-dithiones 11, respectively, depending on the reaction conditions. The structures of 3aa, 4aa, 10a, and 11a were established by X-ray crystallography. All attempts to prepare S-containing morpholine-2,5-dione analogs or thiomorpholine-2,5-diones by cyclization of corresponding S-containing precursors were unsuccessful and led to various other products. The structures of some of them have also been established by X-ray crystallography.
(±)-6-benzyl-3,3-dimethylmorpholine- 2,5-dione and its 5-monothio and 2,5-dithio derivatives
Linden, Anthony,Ghorbani-Salman Pour, Fatemeh,Breitenmoser, Roland A.,Heimgartner, Heinz
, p. 634 - 637 (2007/10/03)
The morpholine ring of the title dione, C13H15NO3, shows a boat conformation that is distorted towards a twist-boat, with the boat ends being the two Csp3 atoms of the ring. The benzyl substituent is in the favoured 'exo' position. In the monothione derivative, (±)-6-benzyl-3,3-dimethyl-5-thioxomorpholin-2-one, C13H15NO2S, this ring has a much flatter conformation that is midway between a boat and an envelope, with the dimethyl end being almost planar. The orientation of the benzyl group is 'endo'. The dithione derivative, (±)-6-benzyl-3,3-dimethylmorpholine-2,5-dithione, C13H15NOS2, has two symmetry-independent molecules, which show different puckering of the morpholine ring. One molecule has a flattened envelope conformation distorted towards a screw-boat, while the conformation in the other molecule is similar to that in the monothione derivative. Intermolecular hydrogen bonds link the molecules in the three compounds, respectively, into centrosymmetric dimers, infinite chains, and dimers made up of one of each of the symmetry-independent molecules.
3-(Dimethylamino)-2,2-dimethyl-2H-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amide Cyclization
Obrecht, Daniel,Heimgartner, Heinz
, p. 329 - 338 (2007/10/02)
In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine (1) and α-hydroxycarboxylic acids react to give diamides of type 8.Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H2O leads to the corresponding carboxylic acids 13.In toluene/PhSH, phenyl thioesters of type 11 are formed.Starting with diamides 8, the formation of morpholin-2,5-diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11.Reaction of carboxylic acids with 1, followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units.Cyclization of 14a, 17a, and 20a with HCl in toluene at 100 deg C gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18, and 21, respectively.
