An expeditious and greener one-pot synthesis of 4H-chromenes catalyzed by Ba(OTf)₂ in PEG-water

Figures & data

Scheme 1.  Synthesis of 4H-chromene-3-carbonitriles.

Table 1. Ba(OTf)₂ catalyzed one-pot synthesis of 4H-chromene-3-carbonitrile (4a) in different solvents.^a

Entry	Solvent	Time (min)	Yield^b (%)
1	DMF	30	60
2	DMSO	30	58
3	1,2-DCE^c	60	–^d
4	Toluene	60	–^d
5	THF	60	–
6	ACN^c	60	–
7	Ethanol	60	–
8	PEG-400	30	60
9	H2O	30	40^e
10	PEG:H2O (50:50)	30	96^f
11	PEG:H2O (70:30)	30	88
12	PEG:H2O (30:70)	30	70
^aReaction conditions: 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), malononitrile (1.0 mmol), Ba(OTf)2 (0.20 mmol), solvent (2.0 mL), room temperature.
^bIsolated yield.
^cDCE, 1,2-dichloroethane; ACN, acetonitrile.
^dOnly intermediate.
^eIn absence of catalyst yield was 30%.
^fIn absence of catalyst yield was 55%.

Table 2. Synthesis of 2-amino-5,6,7,8-tetrahydro-5-oxo-4-(4-chlorophenyl)-4H-chromene-3-carbonitrile with different catalysts in PEG-water (4a).^a

Entry	Catalyst	Time (min)	Yield^b (%)
1	Ho(OTf)3	60	64
2	Yb(OTf)3	30	83
3	Ce(OTf)3	60	66
4	Nd(OTf)3	60	85
5	Sc(OTf)3	30	82
6	Eu(OTf)3	30	87
7	Cu(OTf)2	30	86
8	Zn(OTf)2	30	88
9	Ba(OTf)2	30	96
10	TfOH	30	35
^aReaction conditions: 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), malononitrile (1.0 mmol), Ba(OTf)2 (0.20 mmol), PEG-water (50:50) (2 mL), room temperature.
^bIsolated yield.

Table 3. Effect of catalyst concentration on synthesis of 4H-chromene-3-carbonitrile^a (4a).

Entry	Catalyst (% mmol)	Time (min)	Yield (%)^b
1	1	60	55
2	5	60	68
3	10	30	80
4	20	30	96
5	30	30	94
^aReaction conditions: 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), malononitrile (1.0 mmol), PEG-water (50:50) (2 mL), room temperature.
^bIsolated yield.

Table 4. Synthesis of substituted 4H-chromene derivatives (4a-r) catalyzed by Ba(OTf)₂.^a

						Melting point (°C)
Entry	R	R1	Product (4)^b	Time (min)	Yield (%)^c	Found	Lit. [Ref.]
A	4-Cl	CH3		30	96	212–215	215–217 52
B	4-Me	CH3		30	82	219–221	214–216 (27)
C	4-OMe	CH3		40	84	197–199	199–201 (27)
D	3-Cl	CH3		30	84	226–228	231–233 52
E	3-OMe	CH3		40	86	200–201	-
F	4-NO2	CH3		30	82	182–184	177–178 (27)
G	3-NO2	CH3		30	88	213–215	211–214 52
H	4-CH3	CH3		50	76	222–224	–
I	H	CH3		30	88	227–229	226–228 (36)
J	4-Cl	H		40	87	233–235	228–230 (46)
K	3-NO2	H		40	91	234–236	199–200 (44)
L	4-Me	H		40	82	224–226	224–226 (44)
M	3-OMe	H		40	84	212–214	–
N	4-OMe	H		40	86	206–208	196–198 (44)
O	3-Cl	H		30	90	242–244	–
^aReaction conditions: Aldehyde (1.0 mmol), 1,3-diketone (1.0 mmol), malononitrile (1.0 mmol), Ba(OTf)2 (0.20 mmol), PEG-water (50:50)(2 mL), room temperature.
^bAll products were characterized by IR, ESI-mass, ^1H NMR and ^13C NMR data.
^cIsolated yield by column chromatography on silica gel (60–120 mesh).

Table 5. Recycling of catalyst Ba(OTf)₂ for the synthesis of 4a.^a

Cycle	1	2	3	4	5
Yield (%)^b	96	93	95	92	91
^aReaction conditions: 4-chlorobenzaldehyde (1.0 mmol), dimedone (1.0 mmol), malononitrile (1.0 mmol), Ba(OTf)2 (0.20 mmol), PEG-water (50:50) (2 mL), room temperature.
^bIsolated yield.

Zhi , H .; Lue , C .; Zhang , Q .; Luo , J . Chem. Commun . 2009 , 2878 .

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