1,4-Diacetylpiperazine-2,5-dione, condensation with aldehydes

It has been reported that KF/alumina is a useful catalyst for the condensation of l,4-diacetylpiperazine-2,5-dione with aldehydes under micro-wave irradiation (90SC3325). High yields of the mono- or bis-arylidene derivatives having the Z-configuration have been obtained. 

Reactions of piperazine-2,5-diones with phosphorus pentachloride and phosphorus pentabromide have been described in Sections V.ID and V.IF, respectively. Aromatic aldehydes condense with 3-methylpiperazine-2,5-dione in the presence of acetic anhydride to form mainly mono-A -acetyl derivatives of trans-3-arylidene-6-methylpiperazine-2,5-diones (e.g., 96, R = Ac) (1066). In these products the acetyl group was shown to be attached to position 1 and the 4,5-amide group was found to be sterically hindered. Photolysis formed the cis isomers. Both isomers were deacetylated with methanolic potassium hydroxide (1066). Condensation of 1,4-diacetylpiperazine-2,5-diones with aldehydes has been applied to the synthesis of unsymmetrical 3,6-diarylidenepiperazine-2,5-diones and the reaction has been extended to l,4-diacetyl-3,6-dimethylpiperazine-2,5-diones (1624). Treatment of (96, R = H) with triethyloxonium tetrafluoroborate in dichloromethane gave the monoimino ether, 5-benzylidene-6-ethoxy-3-hydroxy-2-methyl-2,5-dihydropyrazine (97) (1066). l-Methylpiperazine-2,5-dione similarly treated gave 5-ethoxy-l-methyl-2-oxo-l,2,3,6-tetrahydropyrazine (which was condensed with anthranilic acid at 150° to 2-methyl-l,2-dihydropyrazino[2,l-fi]quinazoline-3(4/0.6-dione (98) (1625), and l,4-dimethylpiperazine-2,5-dione gave 5-ethoxy-l,4-dimethyl-2-oxo-1,2,3,4-tetrahydropyrazine and 5,5-diethoxy-l,4-dimethylpiperazin-2-one (1626). 

When equivalent amounts of l,4-diacetylpiperazine-2,5-dione (682) and aldehydes were adsorbed on KF/alumina and irradiated by MW, the Z-isomer of the mon-oarylidene products 683 were obtained in 83-100% yield (Scheme 132). The reaction also took place at room temperature in DMF, but the yield was poorer. Further condensation with another aldehyde gave the mixed double condensation products 684 in 70-91% yield (90SC3325). 

Piperazinedione condenses easily with benzaldehyde in the presence of acetic anhydride/sodium acetate to yield 3,6-dibenzylidene-2,5-piperazinedione (343, 344). Analogous preparations have been conducted with heterocyclic and unsaturated aliphatic aldehydes (19), but not with saturated aliphatic aldehydes. The synthesis of alkylidenepiperazine-diones can be realized by condensation of N,N -diacetylpiperazine-diones with aliphatic aldehydes in the presence of potassium t-butoxide (138, 140), conditions also applicable to the synthesis of monoarylidene-piperazinediones. A second condensation is however only possible with aromatic aldehydes. 

Gallina, C., and A. Liberatori Condensation of l,4-Diacetylpiperazine-2,5-dione with Aldehydes. Tetrahedron 30, 667 (1974). 

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