1- Methyl-3-benzylidenepiperazine-2,5-dion

Free dipeptides or their hydrobromide salts can be cyclized to the corresponding cyclodipeptides by heating in phenol (68JOC862). No detectable racemization takes place. The versatility of the method is shown by the synthesis of cyclo(Ser-Tyr), cyclo(Met-Tyr), cyclo(Gly-Trp), etc. Very facile cyclization (on warming in water) of sarcosyldehydrophenyl-alanine to l-methyl-3-fra/is-benzylidenepiperazine-2,5-dione (14) has been reported [70JCS(C)2530]. 

The irans-benzylidene derivative (188), obtained as the major product of condensation of 3-methylpiperazine 2,5-dione and benzaldehyde in the presence of acetic anhydride, undergoes photoisomerization to the cis isomer (191) on irradiation in methanol. Both isomers have been converted into tetrahydropyrazine imino ethers (189) and (192) by treatment with triethyloxonium fluoroborate. The trans compound reacts more slowly and gives a lower yield of imino ether and this is attributed to steric hindrance. Compounds 188 and 191 are de-acetylated on treatment with methanolic 2 N potassium hydroxide. The trans and cis isomers (187) and (190), so produced are converted into 3-benzyl-2,5-dihydroxy-6-methylpyrazine (144) when heated at 100° with sodium hydroxide.384 Treatment of the dichloroacetyl derivative of phenylalanine with methylamine gives l-methyl-3-benzylidenepiperazine 2,5-dione with the stereochemistry shown.384a... 

The 3-benzylidenepiperazine-2,5-dione (97) derived from L-proline and (Z)-2-methyl-4-benzylideneoxazolone has been converted to a pyrazo-line by cycloaddition of diazomethane and then photolyzed to yield a... 

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