A new protocol for Biginelli (or like) reaction under solvent-free grinding method using Fe (NO₃)₃.9H₂O as catalyst

Figures & data

Scheme 1.  Synthesis of 5-unsubstituted 3, 4-dihydropyrimidinone 1.

Table 1. Synthesis of 5-unsubstituted 3,4-dihydropyrimidinone 1 using 0.1 mmol of different catalysts.

Entry	Catalyst	Solvent	Time (hr)	Yield^a (%)
1	Borax	–	2	5
2	BF3.(OEt)2	–	1.5	10
3	H3BO3	–	2	NR
4	Sulfamic acid	–	1.5	10
5	Oxalic acid	–	1.5	8
6	NH4Cl	–	1	NR
7	CAN	–	1	NR
8	FeNO3..9H2O	–	1.5	92
9	Clayfen	–	3	80
10	Mn(OAc)2.4H2O	–	1.5	NR
11	P-TsOH	–	1.5	NR
12	Monmorillonite-KSF	–	1.5	NR
13	I2	–	1.5	NR
14	FeNO3.9H2O	MeOH	12	90
15	FeNO3.9H2O	CH3COCH3	12	75
16	FeNO3.9H2O	CH2Cl2	12	NR
17	FeNO3.9H2O	CHCl3	12	NR
18	FeNO3.9H2O	H2O	12	NR
^aAll solvent-free reactions were carried out under grinding method.

Table 2. Synthesis of 5-unsubstituted 3,4-dihydropyrimidinone 1 and 5-substituted 3,4dihydropyrimidinone 2 derivatives.

						Melting point (°C)
Entry	R	Product^a	X	Yield^b (%)	Time (min)	Found reported 20 30–3537
1	C6H5	1a	O	90	35	244	245–246
2	4-ClC6H4	1b	O	95	75	266	267–269
3	4-MeOC6H4	1c	O	92	1.5 h	258	259–261
4	2-ClC6H4	1d	O	85	25	261–62	260–263
5	3-Br C6H4	1e	O	80	40	257–58	256–58
6	4-OHC6H4	1f	O	90	25	256	255–257
7	3-MeOC6H4	1g	O	92	55	256	257–258
8	4-MeC6H4	1h	O	88	45	249	248–250
9	3,4-(OMe)2 C6H3	1i	O	93	60	244	243–245
10	C6H5	2a	O	95	1 h	202–203	202–204
11	4-NO2C6H4	2b	O	89	2 h	206–208	208–209
12	2-NO2C6H4	2c	O	90	1.5 h	220	218–220
13	3-NO2C6H4	2d	O	93	75	226–227	226–227
14	4-ClC6H4	2e	O	83	45	211–212	213–215
15	4-MeOC6H4	2f	O	98	55	201–202	201–203
16	4-MeC6H4	2g	O	90	1 h	169–170	168–170
17	C6H5 CH = CH	2h	O	94	75	242–243	241–242
18	CH3(CH2)3	2i	O	65	1 h	156–157	157–158
19	CH3(CH2)2	2j	O	70	2 h	153–155	152–154
20	Furyl	2k	O	75	45	202–203	204.5–205
21	C6H5	2l	S	87	30	200–205	205–206
22	4-MeOC6H4	2m	S	83	45	150	152–154
23	3-NO2C6H4	2n	S	80	80	204–206	206–207
24	4-NO2C6H4	2o	S	85	2	108–110	109–111
25	4-ClC6H4	2p	S	81	75	191–192	192–193
26	3,4,5-(OMe)3 C6H4	2q	S	80	1.5	203–205	202–204
^aAll products were characterized by FT-IR, ^1HNMR, CHN analyzer, and also their melting points with that of previous literature.
^bIsolated yield.
^cMelting points are uncorrected.

Scheme 2.  Synthesis of 5-substituted 3, 4-dihydropyrimidinone 2.

Scheme 3.  Possible reaction mechanism

Figure 1.  (a) IR spectra of reaction mixture (acetophenone, anisaldehyde, and urea) at various time intervals, 60 mins (A), 120 mins (B), 3 hr (C), and pure product (D) where region 3000–3500 cm⁻¹ represents splitting of ν_N–H stretching into two peaks and region 1500–1700 cm⁻¹ shows gradual change of ν_{C = O} stretching frequencies. (b) IR spectra of Monmorillonite K-10 (E), Fe (NO₃)₃.9H₂O (F), clayfen (G), and regenerated clayfen (H).

Wang , Z-T. ; Xu , L-W. ; Xia , C-G. ; Wang , H-Q. Tetrahed. Lett . 2004 , 45 , 7951 1953 .

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