Regioselective Friedel-Crafts alkylation of indoles with epoxides using nano MgO

Figures & data

Scheme 1.  Friedel-Crafts alkylation of indoles by epoxides catalyzed by nano MgO.

Figure 1.  X-Ray diffraction (XRD) image of nano MgO.

Figure 2.  (a) SEM and (b) TEM images of nano MgO.

Table 1. Optimized Friedel-Crafts alkylation reaction of indole (1 mmol) with glycidyl phenyl ether (1 mmol) using nano MgO under various reaction conditions after 8h.

Entry	mmol of nano MgO	Solvent/T (°C)	Yield (%)^a
1	0.5	None/100	70
2	0.5	None/80	50
3	0.5	Toluene/reflux	25
4	0.5	H2O/reflux	15
5	0.5	CH3CN/reflux	15
6	0.5	CH2Cl2/reflux	>60
7	0.5	THF/reflux	35
8	1	None/100	70
9	0.3	None/100	60
10	0.1	None/100	50
11	0.05	None/100	50
^aIsolated yields.

Table 2. Friedel-Crafts alkylation of indoles with epoxides using nano MgO under solvent-free condition at 100°C.

Entry	Epoxide	Indole	Product	Time (h)/yield (%)^a
1				8/70
2		2a		10/65
3		2a		15/60
4		2a		8/60
5^b		2a		24/50
6		2a		12/70
7		2a		12/70
8		2a		6/90
9	1h			6/85
10	1h			6/90
11	1h			8/60
12	1h			6/85
^aYields were determined by GC.
^bDue to its low boiling point, excess amount of 2-methyloxirane was used at room temperature.

Table 3. Friedel-Crafts alkylation of indole with glycidyl phenyl ether under various reported methods.^a

Entry	Catalyst/T (°C)	Solvent	Time (h)	Yield (%)^b
1	Nano MgO/100	None	8	70
2	Nano TiO2 (29)/rt	CH2Cl2	12	0
3	Sulfated zirconia/rt (2)	CH2Cl2	4.5	44
4	SiO2/65/10Kbar (30)	CH3CN	3 days	16
5	HBF4–SiO2/rt (28)	CH2Cl2	2	0
6	SbCl3/K-10 (20)/rt	None	1	58
7	Commercial MgO^c/100	None	15	40
8	Commercial TiO2 ^c/100	None	24	trace
9	Nano ZnO (47, 49)/100	None	15	20
10	Commercial ZnO^c/100	None	15	trace
^aReaction conditions: glycidyl phenyl ether (1 mmol), indole (1 mmol), and catalyst (0.5 mmol).
^bIsolated yields.
^cThe specific surface areas of commercial MgO, TiO2, and ZnO were 10–40, 15–30, and 2.5–12 m^2/g, respectively.

Table 4. Reuse ability of recovered nano MgO.^a

Run	Isolated yield (%)^b	Recycle number
1	70	1
2	70	2
3	70	3
4	68	4
5	68	5
^aReaction condition: phenyl glycidyl ether (5 mmol), indole (5 mmol), nano MgO (2.5 mmol, 0.1 g), solvent-free.
^bIsolated yield.

short-legendScheme 2. Proposed mechanism.