An Efficient One-Pot Multicomponent Synthesis of 4-Aza-Podophyllotoxin Derivatives in Ionic Liquid

Table 5

Synthesis of 4-aza-podophyllotoxin derivatives (4a–r) ^a.

Entry	R	R1	R2	Product	Yield (%)^b	Lit. Mp (°C)	Found Mp (°C)
4a	4-Cl	H	p-CH3		92	274-275	275-276
4b	H	H	p-CH3		91	280-281	281-282
4c	4-CH3O	H	p-CH3		93	254-255	255–257
4d	4-Br	H	H		89	280-281	281-282
4e	4-CH3	H	p-CH3		93	263-264	264–266
4f	H	H	H		90	275-276	276-277
4g	4-Cl	H	p-Cl		92	227-228	228–230
4h	4-CH3O	CH3	p-CH3		95	256-257	257-258
4i	4-Br	CH3	p-CH3		94	269-270	271–273
4j	3-NO2	CH3	p-CH3		92	232-233	232-233
4k	4-Cl	CH3	H		94	260-261	262-263
4l	4-CH3O	CH3	H		92	258-259	260–262
4m	3-NO2	CH3	H		89	293-294	294-295
4n	4-Cl	CH3	p-Cl		93	>300	>300
4o	4-CH3	CH3	p-F		93	281–283	283–285
4p	4-Cl	CH3	p-F		92	297–299	299-300
4q	4-Br	CH3	p-F		88	283–285	285–287
4r	4-OCH3	CH3	p-F		92	266–268	268–270

aReaction conditions: benzaldehydes 1 (1 mmol), cyclohexanediones 2 (1 mmol), and anilinolactones 3 (1 mmol), IL (0.2 mL), alum (20 mol%), at 90°C.
bIsolated yields.