An efficient synthesis of hemiaminal of indoles by using tetrabutylammonium fluoride (TBAF) in water as a reusable reaction media

Figures & data

Scheme 1.  Optimization of reaction condition.

Table 1. Optimization of reaction condition for the synthesis of Hemiaminal 3a^a.

Entry	Additive	Mol% of additive	Solvent	Time (h)	Yield^b of 3a (%)
1	–	–	Water	12	Trace
2	TBAF	10	Water	2	94
3	TBAF	10	CH2Cl2	2	–^c
4	TBAF	10	MeCN	2	23
5	TBAF	10	MeOH	2	32
6	TBAF	10	DMSO	2	38
7	TBAF	10	DMF	2	42
8	CsF	10	Water	2	19
9	KF	10	Water	2	17
10	LiF	10	Water	2	24
11	NH4F	10	Water	2	28
12	TBAF	20	Water	2	94
13	TBAF	40	Water	2	95
^aReactions condition: 1a (1 mmol), 2 (1 ml, 37% aqueous formaldehyde solution), solvent (5 ml), room temperature.
^bIsolated yields.
^c23% C-3 hydroxymethylated product was obtained.

Table 2. Synthesis of hemiaminals of indole derivatives by using TBAF in water as reusable reaction media^a.

Entry	Indole (1a–m)	Time (h)	Product	Yield^b (%)
1		1.8		94
2		1.8		94
3		1.8		91
4		1.8		89
5		1.8		91
6		1.8		90
7		1.8		94
8		1.8		95
9		1.8		93
10		1.8		91
11		1.8		96
12		1.8		90
13		1.8		84
^aReactions condition: 1(a–m) (1 mmol), 2 (1 ml, 37% aqueous formaldehyde solution), TBAF (10 mol%), water (5 ml), room temperature.
^b Isolated yields.

Scheme 2.  Study on the reuse of reaction media.

Table 3. Study on the reuse of reaction media for the synthesis of hemiaminal^a.

Cycle	Time (h)	Yield^b of 3g (%)
1	1.8	94
2	2	94
3	2	92
4	2	90
5	5.2	91
^aReactions condition: 1 g (10 mmol), 2 (10 ml, 37% aqueous formaldehyde solution), TBAF (10 mol%), water (50 ml), room temperature.
^bIsolated yields.