An efficient one-pot synthesis of 1,4-dihydropyridine derivatives through Hantzsch reaction catalysed by melamine trisulfonic acid

Peer review under responsibility of Taibah University.

Figures & data

Scheme 1 Preparation of melamine trisulfonic acid.

Table 1 Optimization of solvent for the synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline.^a

Entry	Solvent	Amount of catalyst (mol%)	Time (h)	Yield (%)^b
1	Methanol	5	5	68
2	1,4-Dioxane	5	8	59
3	Ethanol	5	4	82
4	Cyclohexane	5	10	50
5	Acetonitrile	5	4	72
6	Toluene	5	10	45
7	No solvent	5	3	94

a Reaction conditions: benzaldehyde (2 mmol), dimedone (2 mmol), malononitrile (2 mmol) and ammonium acetate (3 mmol) in the presence of MTSA (5 mol%) at 60 °C.

b Isolated yields.

Table 2 Optimization of catalyst for the synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline.^a

Entry	MTSA (mol%)	Time (h)	Yield (%)^b
1	0.5	5	45
2	1.0	5	57
3	2.0	4	66
4	3.0	4	77
5	4.0	3	86
6	5.0	3	94
7	6.0	3	88

a Reaction conditions: benzaldehyde (2 mmol), dimedone (2 mmol), malononitrile (2 mmol) and ammonium acetate (3 mmol) in the presence of MTSA (5 mol%) at 60 °C.

b Isolated yields.

Table 3 The effect of recyclability of MTSA catalyst for the synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline.^a

Entry	Cycle	Time (h)	Yield (%)^b
1	0	3.0	94
2	1	3.0	92
3	2	3.0	90
4	3	3.0	88

a Reaction conditions: benzaldehyde (2 mmol), dimedone (2 mmol), malononitrile (2 mmol) and ammonium acetate (3 mmol) in the presence of MTSA (5 mol%) at 60 °C.

b Isolated yields.

Fig. 1 Recyclability of MTSA catalyst for the synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline. The catalyst MTSA reused four times.

Table 4 Synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives in the presence of MTSA (5 mol%).^a

Entry	Aldehyde	Product	Time (h)	Yield^b (%)	Mp (°C)
					Found	Reported
1		4a	3.0	94	276–278	275–277 [12]
2		4b	3.5	90	282–284	–
3		4c	3.5	95	286–288	–
4		4d	2.5	88	293–295	294–295 [12]
5		4e	2.5	89	288–290	288–289 [12]
6		4f	3.5	95	292–294	293–294 [12]
7		4g	3.5	91	274–276	–
8		4h	3.5	92	286–288	287–288 [12]
9		4i	3.0	90	268–270	–
10		4j	3.5	88	266–268	–
11		4k	3.0	91	284–286	–
12		4l	3.5	90	270–272	–

a Reaction conditions: arylaldehyde (2 mmol), dimedone (2 mmol), malononitrile (2 mmol) and ammonium acetate (3 mmol) in the presence of MTSA (5 mol%) under solvent free condition. All reactions were carried out at 60 °C.

b Isolated yield.

Scheme 2 Synthesis of 2-amino-4-phenyl-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives in the presence of MTSA (5 mol%) as catalyst at 60 °C under solvent free conditions.

Fig. 2 (A) ¹H NMR spectra of 2-amino-4-(3-nitrophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline (4g). (B) ¹H NMR spectra of 2-amino-4-(3-nitrophenyl)-3-cyano-7,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline (4g).