Three-Component Synthesis of Pyrimidine and Pyrimidinone Derivatives in the Presence of High-Surface-Area MgO, a Highly Effective Heterogeneous Base Catalyst

Figures & data

Scheme 1 Three component reactions of aldehydes, amidine systems, and malonitrile or ethyl cyanoacetate in the presence of magnesium oxide (MgO).

Table 1. Solvent effects on the synthesis of compounds and

Compound	Solvent	Time (min)	Yield (%)
4a	EtOH/H2O	30	72
4a	MeOH	25	78
4a	MeCN	20	85
5a	EtOH/H2O	50	76
5a	MeOH	45	79
5a	MeCN	40	82

Table 2. Knoevenagel condensation of aldehydes with malononitrile or ethyl cyanoacetate catalyzed by MgO in CH₃CN

Compound	Ar	X	Time (min)	Yield (%)	MP [Ref.] (°C)
6a	C6H5	CN	5	94	82–83^[ ^15 ^]
6b	C6H5	CO2Et	10	90	48–50^[ ^15 ^]
6c	4-ClC6H4	CN	5	96	158^[ ^16 ^]
6d	4-ClC6H4	CO2Et	8	91	93^[ ^16 ^]
6e	4-O2NC6H4	CN	4	98	160^[ ^17 ^]
6f	4-O2NC6H4	CO2Et	7	92	170^[ ^17 ^]

Table 3. Michael additions of with amidines catalyzed by MgO in CH₃CN

Compound	Ar	R	Time (min)	Yield (%)
4a	C6H5	C6H5	18	90
4b	C6H5	NH2	13	92
5a	C6H5	C6H5	26	97
4h	4-ClC6H4	C6H5	13	96
4i	4-ClC6H4	NH2	11	97
5b	4-ClC6H4	C6H5	32	95

Table 4. Synthesis of and under thermal conditions without catalyst and in the presence MgO as a highly effective heterogeneous base catalyst

			Thermal conditions		Commercially available MgO		High-surface-area MgO
Compound	Ar	R	Time (h)	Yield (%)	Time (min)	Yield (%)	Time (min)	Yield (%)
4a	C6H5	Ph	6	78	60	83	20	85
4b	C6H5	NH2	5	81	55	86	15	88
4c	4-MeC6H4	Ph	4	79	65	81	20	83
4d	4-MeC6H4	NH2	5	64	60	84	22	86
4e	4-MeOC6H4	Ph	8	60	70	80	30	82
4f	4-(Me)2N C6H4	Ph	12	78	90	80	40	83
4g		Ph	6	46	70	65	30	70
4h	4-ClC6H4	Ph	4	73	50	87	15	89
4i	4-ClC6H4	NH2	3	82	45	90	13	91
4j	4-BrC6H4	Ph	4	80	58	84	18	87
4k	4-BrC6H4	NH2	4	78	52	87	15	89
4l	4-FC6H4	NH2	4	63	48	88	14	90
4m	4-FC6H4	Ph	4	66	45	91	12	92
4n	3-FC6H4	Ph	3	80	50	87	10	90
4o	3-FC6H4	NH2	4	68	45	92	8	96
4p	3-FC6H4	Me	5	60	60	83	20	85
4q	4-CF3C6H4	Ph	2	70	53	83	17	88
4r	4-CF3C6H4	NH2	4	72	50	87	15	90
4s	4-CF3C6H4	Me	5	60	65	80	25	83
5a	C6H5	ph	—	—	120	80	40	82
5b	4-ClC6H4	ph	—	—	110	84	35	85
5c	3-FC6H4	ph	—	—	100	84	33	86
5d	4-CF3C6H4	ph	—	—	110	82	36	84
5e	2,4-ClC6H3	ph	—	—	105	86	33	88
5f	4-NO2C6H4	ph	—	—	100	87	33	89

Scheme 2 Mechanism for the formation of compounds 4 and 5.

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